varsim 1.0.4__tar.gz → 1.0.5__tar.gz

{varsim-1.0.4/src/varsim.egg-info → varsim-1.0.5}/PKG-INFO

@@ -1,6 +1,6 @@
 Metadata-Version: 2.4
 Name: varsim
-Version: 1.0.4
+Version: 1.0.5
 Summary: Variant Simulator
 Author-email: Liu Sun <sunliu@yxnu.edu.cn>, Jian Yang <yangjian@yxnu.edu.cn>
 Project-URL: Homepage, https://github.com/liu-sun/VarSim

{varsim-1.0.4 → varsim-1.0.5}/pyproject.toml

@@ -4,7 +4,7 @@ build-backend = "setuptools.build_meta"
 
 [project]
 name = "varsim"
-version = "1.0.4"
+version = "1.0.5"
 authors = [
   { name="Liu Sun", email="sunliu@yxnu.edu.cn" },
   { name="Jian Yang", email="yangjian@yxnu.edu.cn" },

varsim-1.0.5/src/varsim/__init__.py

@@ -0,0 +1,433 @@
+import os
+
+from Bio import Entrez, SeqIO
+from Bio.Data.CodonTable import standard_dna_table
+from Bio.Data.IUPACData import (
+    unambiguous_dna_letters,
+    protein_letters,
+    protein_letters_1to3,
+    protein_letters_3to1,
+)
+from Bio.Seq import Seq
+from Bio.SeqFeature import SimpleLocation
+from Bio.SeqUtils import seq3
+
+Entrez.email = os.environ["EMAIL"]
+Entrez.api_key = os.environ["API_KEY"]
+codons = standard_dna_table.forward_table.keys()
+
+
+def cds(gene: str) -> list:
+    variants = []
+    stream = Entrez.esearch(
+        db="nucleotide",
+        term=f'{gene}[Gene Name] "mane select"[Keyword]',
+    )
+    record = Entrez.read(stream)
+    stream = Entrez.efetch(
+        db="nucleotide", id=record["IdList"], rettype="gb", retmode="text"
+    )
+    seqrecord = SeqIO.read(stream, "genbank")
+    for feature in seqrecord.features:
+        if feature.type == "CDS":
+            protein = "".join(feature.qualifiers.get("translation"))
+            protein_id = "".join(feature.qualifiers.get("protein_id"))
+            cds = feature.extract(seqrecord).seq
+    for index, codon in enumerate(range(0, len(cds) - 3, 3)):
+        for base in unambiguous_dna_letters:
+            if base != cds[codon]:
+                seq = Seq(base) + cds[codon + 1 : codon + 3]
+                if protein[index] != seq.translate():
+                    variants.append(
+                        (
+                            f"{seqrecord.id}:c.{codon + 1}{cds[codon]}>{base}",
+                            f"{protein_id}:p.{protein[index]}{index + 1}{seq.translate()}",
+                            f"{protein_id}:p.{seq3(protein[index])}{index + 1}{seq3(seq.translate())}",
+                        )
+                    )
+                else:
+                    variants.append(
+                        (
+                            f"{seqrecord.id}:c.{codon + 1}{cds[codon]}>{base}",
+                            f"{protein_id}:p.{protein[index]}{index + 1}=",
+                            f"{protein_id}:p.{seq3(protein[index])}{index + 1}=",
+                        )
+                    )
+            if base != cds[codon + 1]:
+                seq = cds[codon] + Seq(base) + cds[codon + 2]
+                if protein[index] != seq.translate():
+                    variants.append(
+                        (
+                            f"{seqrecord.id}:c.{codon + 2}{cds[codon + 1]}>{base}",
+                            f"{protein_id}:p.{protein[index]}{index + 1}{seq.translate()}",
+                            f"{protein_id}:p.{seq3(protein[index])}{index + 1}{seq3(seq.translate())}",
+                        )
+                    )
+                else:
+                    variants.append(
+                        (
+                            f"{seqrecord.id}:c.{codon + 2}{cds[codon + 1]}>{base}",
+                            f"{protein_id}:p.{protein[index]}{index + 1}=",
+                            f"{protein_id}:p.{seq3(protein[index])}{index + 1}=",
+                        )
+                    )
+            if base != cds[codon + 2]:
+                seq = cds[codon : codon + 2] + Seq(base)
+                if protein[index] != seq.translate():
+                    variants.append(
+                        (
+                            f"{seqrecord.id}:c.{codon + 3}{cds[codon + 2]}>{base}",
+                            f"{protein_id}:p.{protein[index]}{index + 1}{seq.translate()}",
+                            f"{protein_id}:p.{seq3(protein[index])}{index + 1}{seq3(seq.translate())}",
+                        )
+                    )
+                else:
+                    variants.append(
+                        (
+                            f"{seqrecord.id}:c.{codon + 3}{cds[codon + 2]}>{base}",
+                            f"{protein_id}:p.{protein[index]}{index + 1}=",
+                            f"{protein_id}:p.{seq3(protein[index])}{index + 1}=",
+                        )
+                    )
+    return variants
+
+
+def utr5(gene: str) -> list:
+    variants = []
+    stream = Entrez.esearch(
+        db="nucleotide",
+        term=f'{gene}[Gene Name] "mane select"[Keyword]',
+    )
+    record = Entrez.read(stream)
+    stream = Entrez.efetch(
+        db="nucleotide", id=record["IdList"], rettype="gb", retmode="text"
+    )
+    seqrecord = SeqIO.read(stream, "genbank")
+    for feature in seqrecord.features:
+        if feature.type == "CDS":
+            utr5 = SimpleLocation(0, feature.location.start).extract(seqrecord).seq
+    for index in range(len(utr5)):
+        for base in unambiguous_dna_letters:
+            if base != utr5[index]:
+                variants.append(
+                    (
+                        f"{seqrecord.id}:c.{index - len(utr5)}{utr5[index]}>{base}",
+                        "",
+                        "",
+                    )
+                )
+    return variants
+
+
+def utr3(gene: str) -> list:
+    variants = []
+    stream = Entrez.esearch(
+        db="nucleotide",
+        term=f'{gene}[Gene Name] "mane select"[Keyword]',
+    )
+    record = Entrez.read(stream)
+    stream = Entrez.efetch(
+        db="nucleotide", id=record["IdList"], rettype="gb", retmode="text"
+    )
+    seqrecord = SeqIO.read(stream, "genbank")
+    for feature in seqrecord.features:
+        if feature.type == "CDS":
+            utr3 = (
+                SimpleLocation(feature.location.end, len(seqrecord))
+                .extract(seqrecord)
+                .seq
+            )
+    for index in range(len(utr3)):
+        for base in unambiguous_dna_letters:
+            if base != utr3[index]:
+                variants.append(
+                    (
+                        f"{seqrecord.id}:c.*{index + 1}{utr3[index]}>{base}",
+                        "",
+                        "",
+                    )
+                )
+    return variants
+
+
+def splicing(gene: str) -> list:
+    variants = []
+    exon = []
+    stream = Entrez.esearch(
+        db="nucleotide", term=f'{gene}[Gene Name] "mane select"[Keyword]'
+    )
+    record = Entrez.read(stream)
+
+    stream = Entrez.efetch(
+        db="nucleotide", id=record["IdList"], rettype="gb", retmode="text"
+    )
+    seqrecord = SeqIO.read(stream, "genbank")
+    splicing = []
+    variants = []
+    start = 0
+    end = 0
+    for feature in seqrecord.features:
+        if feature.type == "CDS":
+            start = feature.location.start
+            end = feature.location.end
+    for feature in seqrecord.features:
+        if feature.type == "exon":
+            if feature.location.start < start and feature.location.end < start:
+                splicing.extend(
+                    (
+                        feature.location.start - start - 1,
+                        feature.location.end - start - 1,
+                    )
+                )
+            elif feature.location.start < start and feature.location.end > start:
+                splicing.extend(
+                    (feature.location.start - start - 1, feature.location.end - start)
+                )
+            else:
+                splicing.extend(
+                    (feature.location.start - start, feature.location.end - start)
+                )
+
+    for coordinate in range(1, len(splicing) - 1, 2):
+        site = splicing[coordinate], splicing[coordinate] + 1
+        for base in unambiguous_dna_letters:
+            if base != "G":
+                variants.append((f"{seqrecord.id}:c.{site[0]}+1G>{base}"))
+            if base != "T":
+                variants.append((f"{seqrecord.id}:c.{site[0]}+2T>{base}"))
+            if base != "A":
+                variants.append((f"{seqrecord.id}:c.{site[1]}-2A>{base}"))
+            if base != "G":
+                variants.append((f"{seqrecord.id}:c.{site[1]}-1G>{base}"))
+    return variants
+
+
+def aa_sub(gene: str) -> list:
+    variants = []
+    term = f'{gene}[Gene Name] AND "mane select"[keyword]'
+    stream = Entrez.esearch(db="protein", term=term)
+    record = Entrez.read(stream)
+
+    stream = Entrez.efetch(
+        db="protein", rettype="gp", retmode="text", id=record["IdList"]
+    )
+    seqrecord = SeqIO.read(stream, "genbank")
+    for index, residue in enumerate(seqrecord.seq, 1):
+        for aa in protein_letters:
+            if aa != residue:
+                variants.append(
+                    (
+                        f"{seqrecord.id}:p.{residue}{index}{aa}",
+                        f"{seqrecord.id}:p.{protein_letters_1to3[residue]}{index}{protein_letters_1to3[aa]}",
+                    )
+                )
+    return variants
+
+
+def missense(gene: str) -> list:
+    variants = []
+    term = f'{gene}[Gene Name] "mane select"[keyword]'
+    stream = Entrez.esearch(db="nucleotide", term=term)
+    record = Entrez.read(stream)
+    stream = Entrez.efetch(
+        db="nucleotide", id=record["IdList"], rettype="gb", retmode="text"
+    )
+    seqrecord = SeqIO.read(stream, "genbank")
+    for feature in seqrecord.features:
+        if feature.type == "CDS":
+            protein = "".join(feature.qualifiers.get("translation"))
+            protein_id = "".join(feature.qualifiers.get("protein_id"))
+            cds = feature.location.extract(seqrecord).seq
+    for index, codon in enumerate(range(0, len(cds) - 3, 3)):
+        for base in codons:
+            if base != cds[codon : codon + 3]:
+                seq = Seq(base)
+                if protein[index] != seq.translate():
+                    if (
+                        base[0] == cds[codon]
+                        and base[1] == cds[codon + 1]
+                        and base[2] != cds[codon + 2]
+                    ):
+                        variants.append(
+                            (
+                                f"{seqrecord.id}:c.{codon + 3}{cds[codon + 2]}>{base[2]}",
+                                f"{protein_id}:p.{protein[index]}{index + 1}{seq.translate()}",
+                                f"{protein_id}:p.{seq3(protein[index])}{index + 1}{seq3(seq.translate())}",
+                            )
+                        )
+                    elif (
+                        base[0] == cds[codon]
+                        and base[1] != cds[codon + 1]
+                        and base[2] == cds[codon + 2]
+                    ):
+                        variants.append(
+                            (
+                                f"{seqrecord.id}:c.{codon + 2}{cds[codon + 1]}>{base[1]}",
+                                f"{protein_id}:p.{protein[index]}{index + 1}{seq.translate()}",
+                                f"{protein_id}:p.{seq3(protein[index])}{index + 1}{seq3(seq.translate())}",
+                            )
+                        )
+                    elif (
+                        base[0] != cds[codon]
+                        and base[1] == cds[codon + 1]
+                        and base[2] == cds[codon + 2]
+                    ):
+                        variants.append(
+                            (
+                                f"{seqrecord.id}:c.{codon + 1}{cds[codon]}>{base[0]}",
+                                f"{protein_id}:p.{protein[index]}{index + 1}{seq.translate()}",
+                                f"{protein_id}:p.{seq3(protein[index])}{index + 1}{seq3(seq.translate())}",
+                            )
+                        )
+                    else:
+                        variants.append(
+                            (
+                                f"{seqrecord.id}:c.{codon + 1}_{codon + 3}{cds[codon:codon + 3]}>{base}",
+                                f"{protein_id}:p.{protein[index]}{index + 1}{seq.translate()}",
+                                f"{protein_id}:p.{seq3(protein[index])}{index + 1}{seq3(seq.translate())}",
+                            )
+                        )
+                else:
+                    if (
+                        base[0] == cds[codon]
+                        and base[1] == cds[codon + 1]
+                        and base[2] != cds[codon + 2]
+                    ):
+                        variants.append(
+                            (
+                                f"{seqrecord.id}:c.{codon + 3}{cds[codon + 2]}>{base[2]}",
+                                f"{protein_id}:p.{protein[index]}{index + 1}=",
+                                f"{protein_id}:p.{seq3(protein[index])}{index + 1}=",
+                            )
+                        )
+                    elif (
+                        base[0] == cds[codon]
+                        and base[1] != cds[codon + 1]
+                        and base[2] == cds[codon + 2]
+                    ):
+                        variants.append(
+                            (
+                                f"{seqrecord.id}:c.{codon + 2}{cds[codon + 1]}>{base[1]}",
+                                f"{protein_id}:p.{protein[index]}{index + 1}=",
+                                f"{protein_id}:p.{seq3(protein[index])}{index + 1}=",
+                            )
+                        )
+                    elif (
+                        base[0] != cds[codon]
+                        and base[1] == cds[codon + 1]
+                        and base[2] == cds[codon + 2]
+                    ):
+                        variants.append(
+                            (
+                                f"{seqrecord.id}:c.{codon + 1}{cds[codon]}>{base[0]}",
+                                f"{protein_id}:p.{protein[index]}{index + 1}=",
+                                f"{protein_id}:p.{seq3(protein[index])}{index + 1}=",
+                            )
+                        )
+                    else:
+                        variants.append(
+                            (
+                                f"{seqrecord.id}:c.{codon + 1}_{codon + 3}{cds[codon:codon + 3]}>{base}",
+                                f"{protein_id}:p.{protein[index]}{index + 1}=",
+                                f"{protein_id}:p.{seq3(protein[index])}{index + 1}=",
+                            )
+                        )
+    return variants
+
+
+def inframe_del(gene: str) -> list:
+    variants = []
+    term = f'{gene}[Gene Name] "mane select"[keyword]'
+    stream = Entrez.esearch(db="nucleotide", term=term)
+    record = Entrez.read(stream)
+    stream = Entrez.efetch(
+        db="nucleotide", id=record["IdList"], rettype="gb", retmode="text"
+    )
+    seqrecord = SeqIO.read(stream, "genbank")
+    for feature in seqrecord.features:
+        if feature.type == "CDS":
+            protein = "".join(feature.qualifiers.get("translation"))
+            protein_id = "".join(feature.qualifiers.get("protein_id"))
+            cds = feature.location.extract(seqrecord).seq
+    for index, codon in enumerate(range(0, len(cds) - 3, 3)):
+        variants.append(
+            (
+                f"{seqrecord.id}:c.{codon + 1}_{codon + 3}{cds[codon:codon + 3]}del",
+                f"{protein_id}:p.{protein[index]}{index + 1}del",
+                f"{protein_id}:p.{seq3(protein[index])}{index + 1}del",
+            )
+        )
+    return variants
+
+
+def inframe_dup(gene: str) -> list:
+    variants = []
+    term = f'{gene}[Gene Name] "mane select"[keyword]'
+    stream = Entrez.esearch(db="nucleotide", term=term)
+    record = Entrez.read(stream)
+    stream = Entrez.efetch(
+        db="nucleotide", id=record["IdList"], rettype="gb", retmode="text"
+    )
+    seqrecord = SeqIO.read(stream, "genbank")
+    for feature in seqrecord.features:
+        if feature.type == "CDS":
+            protein = "".join(feature.qualifiers.get("translation"))
+            protein_id = "".join(feature.qualifiers.get("protein_id"))
+            cds = feature.location.extract(seqrecord).seq
+    for index, codon in enumerate(range(0, len(cds) - 3, 3)):
+        variants.append(
+            (
+                f"{seqrecord.id}:c.{codon + 1}_{codon + 3}{cds[codon:codon + 3]}dup",
+                f"{protein_id}:p.{protein[index]}{index + 1}dup",
+                f"{protein_id}:p.{seq3(protein[index])}{index + 1}dup",
+            )
+        )
+    return variants
+
+
+def frameshift_dup(gene: str) -> list:
+    variants = []
+    term = f'{gene}[Gene Name] "mane select"[keyword]'
+    stream = Entrez.esearch(db="nucleotide", term=term)
+    record = Entrez.read(stream)
+    stream = Entrez.efetch(
+        db="nucleotide", id=record["IdList"], rettype="gb", retmode="text"
+    )
+    seqrecord = SeqIO.read(stream, "genbank")
+    for feature in seqrecord.features:
+        if feature.type == "CDS":
+            cds = feature.location.extract(seqrecord).seq
+    for index, base in enumerate(cds, start=1):
+        variants.append((f"{seqrecord.id}:c.{str(index) + base}dup",))
+    return variants
+
+
+def frameshift_del(gene: str) -> list:
+    variants = []
+    term = f'{gene}[Gene Name] "mane select"[keyword]'
+    stream = Entrez.esearch(db="nucleotide", term=term)
+    record = Entrez.read(stream)
+    stream = Entrez.efetch(
+        db="nucleotide", id=record["IdList"], rettype="gb", retmode="text"
+    )
+    seqrecord = SeqIO.read(stream, "genbank")
+    for feature in seqrecord.features:
+        if feature.type == "CDS":
+            cds = feature.location.extract(seqrecord).seq
+    for index, base in enumerate(cds, start=1):
+        variants.append((f"{seqrecord.id}:c.{str(index) + base}del",))
+    return variants
+
+
+__all__ = [
+    "frameshift_dup",
+    "frameshift_del",
+    "cds",
+    "inframe_dup",
+    "inframe_del",
+    "splicing",
+    "utr5",
+    "utr3",
+    "aa_sub",
+    "missense",
+]

{varsim-1.0.4 → varsim-1.0.5/src/varsim.egg-info}/PKG-INFO

@@ -1,6 +1,6 @@
 Metadata-Version: 2.4
 Name: varsim
-Version: 1.0.4
+Version: 1.0.5
 Summary: Variant Simulator
 Author-email: Liu Sun <sunliu@yxnu.edu.cn>, Jian Yang <yangjian@yxnu.edu.cn>
 Project-URL: Homepage, https://github.com/liu-sun/VarSim

varsim-1.0.4/src/varsim/__init__.py

@@ -1,270 +0,0 @@
-import os
-
-from Bio import Entrez, SeqIO
-from Bio.Data.CodonTable import standard_dna_table
-from Bio.Data.IUPACData import (unambiguous_dna_letters, protein_letters, protein_letters_1to3, protein_letters_3to1, )
-from Bio.Seq import Seq
-from Bio.SeqFeature import SimpleLocation
-from Bio.SeqUtils import seq3
-
-Entrez.email = os.environ["EMAIL"]
-Entrez.api_key = os.environ["API_KEY"]
-codons = standard_dna_table.forward_table.keys()
-
-
-def cds(gene: str) -> list:
-    variants = []
-    stream = Entrez.esearch(db="nucleotide", term=f'{gene}[Gene Name] "mane select"[Keyword]', )
-    record = Entrez.read(stream)
-    stream = Entrez.efetch(db="nucleotide", id=record["IdList"], rettype="gb", retmode="text")
-    seqrecord = SeqIO.read(stream, "genbank")
-    for feature in seqrecord.features:
-        if feature.type == "CDS":
-            protein = "".join(feature.qualifiers.get("translation"))
-            protein_id = "".join(feature.qualifiers.get("protein_id"))
-            cds = feature.extract(seqrecord).seq
-    for index, codon in enumerate(range(0, len(cds) - 3, 3)):
-        for base in unambiguous_dna_letters:
-            if base != cds[codon]:
-                seq = Seq(base) + cds[codon + 1: codon + 3]
-                if protein[index] != seq.translate():
-                    variants.append((f"{seqrecord.id}:c.{codon + 1}{cds[codon]}>{base}",
-                                     f"{protein_id}:p.{protein[index]}{index + 1}{seq.translate()}",
-                                     f"{protein_id}:p.{seq3(protein[index])}{index + 1}{seq3(seq.translate())}",))
-                else:
-                    variants.append((f"{seqrecord.id}:c.{codon + 1}{cds[codon]}>{base}",
-                                     f"{protein_id}:p.{protein[index]}{index + 1}=",
-                                     f"{protein_id}:p.{seq3(protein[index])}{index + 1}=",))
-            if base != cds[codon + 1]:
-                seq = cds[codon] + Seq(base) + cds[codon + 2]
-                if protein[index] != seq.translate():
-                    variants.append((f"{seqrecord.id}:c.{codon + 2}{cds[codon + 1]}>{base}",
-                                     f"{protein_id}:p.{protein[index]}{index + 1}{seq.translate()}",
-                                     f"{protein_id}:p.{seq3(protein[index])}{index + 1}{seq3(seq.translate())}",))
-                else:
-                    variants.append((f"{seqrecord.id}:c.{codon + 2}{cds[codon + 1]}>{base}",
-                                     f"{protein_id}:p.{protein[index]}{index + 1}=",
-                                     f"{protein_id}:p.{seq3(protein[index])}{index + 1}=",))
-            if base != cds[codon + 2]:
-                seq = cds[codon: codon + 2] + Seq(base)
-                if protein[index] != seq.translate():
-                    variants.append((f"{seqrecord.id}:c.{codon + 3}{cds[codon + 2]}>{base}",
-                                     f"{protein_id}:p.{protein[index]}{index + 1}{seq.translate()}",
-                                     f"{protein_id}:p.{seq3(protein[index])}{index + 1}{seq3(seq.translate())}",))
-                else:
-                    variants.append((f"{seqrecord.id}:c.{codon + 3}{cds[codon + 2]}>{base}",
-                                     f"{protein_id}:p.{protein[index]}{index + 1}=",
-                                     f"{protein_id}:p.{seq3(protein[index])}{index + 1}=",))
-    return variants
-
-
-def utr5(gene: str) -> list:
-    variants = []
-    stream = Entrez.esearch(db="nucleotide", term=f'{gene}[Gene Name] "mane select"[Keyword]', )
-    record = Entrez.read(stream)
-    stream = Entrez.efetch(db="nucleotide", id=record["IdList"], rettype="gb", retmode="text")
-    seqrecord = SeqIO.read(stream, "genbank")
-    for feature in seqrecord.features:
-        if feature.type == "CDS":
-            utr5 = SimpleLocation(0, feature.location.start).extract(seqrecord).seq
-    for index in range(len(utr5)):
-        for base in unambiguous_dna_letters:
-            if base != utr5[index]:
-                variants.append((f"{seqrecord.id}:c.{index - len(utr5)}{utr5[index]}>{base}", "", "",))
-    return variants
-
-
-def utr3(gene: str) -> list:
-    variants = []
-    stream = Entrez.esearch(db="nucleotide", term=f'{gene}[Gene Name] "mane select"[Keyword]', )
-    record = Entrez.read(stream)
-    stream = Entrez.efetch(db="nucleotide", id=record["IdList"], rettype="gb", retmode="text")
-    seqrecord = SeqIO.read(stream, "genbank")
-    for feature in seqrecord.features:
-        if feature.type == "CDS":
-            utr3 = (SimpleLocation(feature.location.end, len(seqrecord)).extract(seqrecord).seq)
-    for index in range(len(utr3)):
-        for base in unambiguous_dna_letters:
-            if base != utr3[index]:
-                variants.append((f"{seqrecord.id}:c.*{index + 1}{utr3[index]}>{base}", "", "",))
-    return variants
-
-
-def splicing(gene: str) -> list:
-    variants = []
-    exon = []
-    stream = Entrez.esearch(db="nucleotide", term=f'{gene}[Gene Name] "mane select"[Keyword]')
-    record = Entrez.read(stream)
-
-    stream = Entrez.efetch(db="nucleotide", id=record["IdList"], rettype="gb", retmode="text")
-    seqrecord = SeqIO.read(stream, "genbank")
-    splicing = []
-    variants = []
-    start = 0
-    end = 0
-    for feature in seqrecord.features:
-        if feature.type == "CDS":
-            start = feature.location.start
-            end = feature.location.end
-    for feature in seqrecord.features:
-        if feature.type == "exon":
-            if feature.location.start < start and feature.location.end < start:
-                splicing.extend((feature.location.start - start - 1, feature.location.end - start - 1,))
-            elif feature.location.start < start and feature.location.end > start:
-                splicing.extend((feature.location.start - start - 1, feature.location.end - start))
-            else:
-                splicing.extend((feature.location.start - start, feature.location.end - start))
-
-    for coordinate in range(1, len(splicing) - 1, 2):
-        site = splicing[coordinate], splicing[coordinate] + 1
-        for base in unambiguous_dna_letters:
-            if base != "G":
-                variants.append((f"{seqrecord.id}:c.{site[0]}+1G>{base}"))
-            if base != "T":
-                variants.append((f"{seqrecord.id}:c.{site[0]}+2T>{base}"))
-            if base != "A":
-                variants.append((f"{seqrecord.id}:c.{site[1]}-2A>{base}"))
-            if base != "G":
-                variants.append((f"{seqrecord.id}:c.{site[1]}-1G>{base}"))
-    return variants
-
-
-def aa_sub(gene: str) -> list:
-    variants = []
-    term = f'{gene}[Gene Name] AND "mane select"[keyword]'
-    stream = Entrez.esearch(db="protein", term=term)
-    record = Entrez.read(stream)
-
-    stream = Entrez.efetch(db="protein", rettype="gp", retmode="text", id=record["IdList"])
-    seqrecord = SeqIO.read(stream, "genbank")
-    for index, residue in enumerate(seqrecord.seq, 1):
-        for aa in protein_letters:
-            if aa != residue:
-                variants.append((f"{seqrecord.id}:p.{residue}{index}{aa}",
-                                 f"{seqrecord.id}:p.{protein_letters_1to3[residue]}{index}{protein_letters_1to3[aa]}",))
-    return variants
-
-
-def missense(gene: str) -> list:
-    variants = []
-    term = f'{gene}[Gene Name] "mane select"[keyword]'
-    stream = Entrez.esearch(db="nucleotide", term=term)
-    record = Entrez.read(stream)
-    stream = Entrez.efetch(db="nucleotide", id=record["IdList"], rettype="gb", retmode="text")
-    seqrecord = SeqIO.read(stream, "genbank")
-    for feature in seqrecord.features:
-        if feature.type == "CDS":
-            protein = "".join(feature.qualifiers.get("translation"))
-            protein_id = "".join(feature.qualifiers.get("protein_id"))
-            cds = feature.location.extract(seqrecord).seq
-    for index, codon in enumerate(range(0, len(cds) - 3, 3)):
-        for base in codons:
-            if base != cds[codon: codon + 3]:
-                seq = Seq(base)
-                if protein[index] != seq.translate():
-                    if (base[0] == cds[codon] and base[1] == cds[codon + 1] and base[2] != cds[codon + 2]):
-                        variants.append((f"{seqrecord.id}:c.{codon + 3}{cds[codon + 2]}>{base[2]}",
-                                         f"{protein_id}:p.{protein[index]}{index + 1}{seq.translate()}",
-                                         f"{protein_id}:p.{seq3(protein[index])}{index + 1}{seq3(seq.translate())}",))
-                    elif (base[0] == cds[codon] and base[1] != cds[codon + 1] and base[2] == cds[codon + 2]):
-                        variants.append((f"{seqrecord.id}:c.{codon + 2}{cds[codon + 1]}>{base[1]}",
-                                         f"{protein_id}:p.{protein[index]}{index + 1}{seq.translate()}",
-                                         f"{protein_id}:p.{seq3(protein[index])}{index + 1}{seq3(seq.translate())}",))
-                    elif (base[0] != cds[codon] and base[1] == cds[codon + 1] and base[2] == cds[codon + 2]):
-                        variants.append((f"{seqrecord.id}:c.{codon + 1}{cds[codon]}>{base[0]}",
-                                         f"{protein_id}:p.{protein[index]}{index + 1}{seq.translate()}",
-                                         f"{protein_id}:p.{seq3(protein[index])}{index + 1}{seq3(seq.translate())}",))
-                    else:
-                        variants.append((f"{seqrecord.id}:c.{codon + 1}_{codon + 3}{cds[codon:codon + 3]}>{base}",
-                                         f"{protein_id}:p.{protein[index]}{index + 1}{seq.translate()}",
-                                         f"{protein_id}:p.{seq3(protein[index])}{index + 1}{seq3(seq.translate())}",))
-                else:
-                    if (base[0] == cds[codon] and base[1] == cds[codon + 1] and base[2] != cds[codon + 2]):
-                        variants.append((f"{seqrecord.id}:c.{codon + 3}{cds[codon + 2]}>{base[2]}",
-                                         f"{protein_id}:p.{protein[index]}{index + 1}=",
-                                         f"{protein_id}:p.{seq3(protein[index])}{index + 1}=",))
-                    elif (base[0] == cds[codon] and base[1] != cds[codon + 1] and base[2] == cds[codon + 2]):
-                        variants.append((f"{seqrecord.id}:c.{codon + 2}{cds[codon + 1]}>{base[1]}",
-                                         f"{protein_id}:p.{protein[index]}{index + 1}=",
-                                         f"{protein_id}:p.{seq3(protein[index])}{index + 1}=",))
-                    elif (base[0] != cds[codon] and base[1] == cds[codon + 1] and base[2] == cds[codon + 2]):
-                        variants.append((f"{seqrecord.id}:c.{codon + 1}{cds[codon]}>{base[0]}",
-                                         f"{protein_id}:p.{protein[index]}{index + 1}=",
-                                         f"{protein_id}:p.{seq3(protein[index])}{index + 1}=",))
-                    else:
-                        variants.append((f"{seqrecord.id}:c.{codon + 1}_{codon + 3}{cds[codon:codon + 3]}>{base}",
-                                         f"{protein_id}:p.{protein[index]}{index + 1}=",
-                                         f"{protein_id}:p.{seq3(protein[index])}{index + 1}=",))
-    return variants
-
-
-def inframe_del(gene: str) -> list:
-    variants = []
-    term = f'{gene}[Gene Name] "mane select"[keyword]'
-    stream = Entrez.esearch(db="nucleotide", term=term)
-    record = Entrez.read(stream)
-    stream = Entrez.efetch(db="nucleotide", id=record["IdList"], rettype="gb", retmode="text")
-    seqrecord = SeqIO.read(stream, "genbank")
-    for feature in seqrecord.features:
-        if feature.type == "CDS":
-            protein = "".join(feature.qualifiers.get("translation"))
-            protein_id = "".join(feature.qualifiers.get("protein_id"))
-            cds = feature.location.extract(seqrecord).seq
-    for index, codon in enumerate(range(0, len(cds) - 3, 3)):
-        variants.append((f"{seqrecord.id}:c.{codon + 1}_{codon + 3}{cds[codon:codon + 3]}del",
-                         f"{protein_id}:p.{protein[index]}{index + 1}del",
-                         f"{protein_id}:p.{seq3(protein[index])}{index + 1}del",))
-    return variants
-
-
-def inframe_dup(gene: str) -> list:
-    variants = []
-    term = f'{gene}[Gene Name] "mane select"[keyword]'
-    stream = Entrez.esearch(db="nucleotide", term=term)
-    record = Entrez.read(stream)
-    stream = Entrez.efetch(db="nucleotide", id=record["IdList"], rettype="gb", retmode="text")
-    seqrecord = SeqIO.read(stream, "genbank")
-    for feature in seqrecord.features:
-        if feature.type == "CDS":
-            protein = "".join(feature.qualifiers.get("translation"))
-            protein_id = "".join(feature.qualifiers.get("protein_id"))
-            cds = feature.location.extract(seqrecord).seq
-    for index, codon in enumerate(range(0, len(cds) - 3, 3)):
-        variants.append((f"{seqrecord.id}:c.{codon + 1}_{codon + 3}{cds[codon:codon + 3]}dup",
-                         f"{protein_id}:p.{protein[index]}{index + 1}dup",
-                         f"{protein_id}:p.{seq3(protein[index])}{index + 1}dup",))
-    return variants
-
-
-def frameshift_dup(gene: str) -> list:
-    variants = []
-    term = f'{gene}[Gene Name] "mane select"[keyword]'
-    stream = Entrez.esearch(db="nucleotide", term=term)
-    record = Entrez.read(stream)
-    stream = Entrez.efetch(db="nucleotide", id=record["IdList"], rettype="gb", retmode="text")
-    seqrecord = SeqIO.read(stream, "genbank")
-    for feature in seqrecord.features:
-        if feature.type == "CDS":
-            cds = feature.location.extract(seqrecord).seq
-    for index, base in enumerate(cds, start=1):
-        variants.append((f"{seqrecord.id}:c.{str(index) + base}dup",))
-    return variants
-
-
-def frameshift_del(gene: str) -> list:
-    variants = []
-    term = f'{gene}[Gene Name] "mane select"[keyword]'
-    stream = Entrez.esearch(db="nucleotide", term=term)
-    record = Entrez.read(stream)
-    stream = Entrez.efetch(db="nucleotide", id=record["IdList"], rettype="gb", retmode="text")
-    seqrecord = SeqIO.read(stream, "genbank")
-    for feature in seqrecord.features:
-        if feature.type == "CDS":
-            cds = feature.location.extract(seqrecord).seq
-    for index, base in enumerate(cds, start=1):
-        variants.append((f"{seqrecord.id}:c.{str(index) + base}del",))
-    return variants
-
-
-if __name__ == "__main__":
-    print(frameshift_del("INS"))