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hgvs_c to hgvs_p projection throws IndexError for "NM_001253909.2:c.416_417insGTG" #707

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holtgrewe opened this issue Oct 21, 2023 · 2 comments · May be fixed by #708
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hgvs_c to hgvs_p projection throws IndexError for "NM_001253909.2:c.416_417insGTG" #707

holtgrewe opened this issue Oct 21, 2023 · 2 comments · May be fixed by #708
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@holtgrewe
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Said variant is a (disruptive) inframe_insertion in the stop codon with stop_retained effect. This corresponds to SPDI GRCh37:10:5139789:A:AGTG.

Based on the current main branch, the following test fails:

diff --git a/tests/test_hgvs_variantmapper.py b/tests/test_hgvs_variantmapper.py
index 63a61ce..dcd5bb4 100644
--- a/tests/test_hgvs_variantmapper.py
+++ b/tests/test_hgvs_variantmapper.py
@@ -39,6 +39,12 @@ class Test_VariantMapper_Exceptions(unittest.TestCase):
         cls.vm = hgvs.variantmapper.VariantMapper(cls.hdp)
         cls.hp = hgvs.parser.Parser()

+    def test_map_stop_retained(self):
+        hgvs_c = "NM_001253909.2:c.416_417insGTG"
+        var_c = self.hp.parse_hgvs_variant(hgvs_c)
+        with self.assertRaises(HGVSInvalidVariantError):
+            self.vm.c_to_p(var_c)
+
     def test_gcrp_invalid_input_type(self):
         hgvs_g = "NC_000007.13:g.36561662C>T"
         hgvs_c = "NM_001637.3:c.1582G>A"

The exception backtrace is as follows:

============================================================================================= test session starts ==============================================================================================
platform linux -- Python 3.10.6, pytest-7.4.2, pluggy-1.3.0 -- /home/holtgrem_c/Development/hgvs/venv/bin/python
cachedir: .pytest_cache
HGVS_CACHE_MODE: learn
HGVS_SEQREPO_URL: None
UTA_DB_URL: postgresql://anonymous:anonymous@uta.biocommons.org:/uta/uta_20210129
hgvs.easy.hdp=postgresql://anonymous:anonymous@uta.biocommons.org:/uta/uta_20210129
hgvs.easy.hdp.seqfetcher.source='bioutils.seqfetcher (network fetching)'
rootdir: /home/holtgrem_c/Development/hgvs
configfile: pytest.ini
plugins: recording-0.13.0, cov-4.1.0, anyio-4.0.0
collected 1 item

tests/test_hgvs_variantmapper.py::Test_VariantMapper_Exceptions::test_map_stop_retained FAILED                                                                                                           [100%]

=================================================================================================== FAILURES ===================================================================================================
_____________________________________________________________________________ Test_VariantMapper_Exceptions.test_map_stop_retained _____________________________________________________________________________
self = <test_hgvs_variantmapper.Test_VariantMapper_Exceptions testMethod=test_map_stop_retained>

    def test_map_stop_retained(self):
        hgvs_c = "NM_001253909.2:c.416_417insGTG"
        var_c = self.hp.parse_hgvs_variant(hgvs_c)
        with self.assertRaises(HGVSInvalidVariantError):
>           self.vm.c_to_p(var_c)

tests/test_hgvs_variantmapper.py:46:
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
src/hgvs/variantmapper.py:447: in c_to_p
    var_p = builder.build_hgvsp()
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
    def build_hgvsp(self):
        """Compare two amino acid sequences; generate an hgvs tag from the output

        :return list of variants in sequence order
        :rtype list of dict
        """

        variants = []

        if not self._is_ambiguous and len(self._alt_seq) > 0:
            do_delins = True
            if self._ref_seq == self._alt_seq:
                # Silent p. variant
                start = self._alt_data.variant_start_aa
                if start - 1 < len(self._ref_seq):
                    deletion = self._ref_seq[start - 1]
                    insertion = deletion
                else:
                    start = ""
                    deletion = ""
                    insertion = ""
                    self._is_frameshift = False
                variants.append({"start": start, "ins": insertion, "del": deletion})
                do_delins = False
            elif self._is_substitution:
                if len(self._ref_seq) == len(self._alt_seq):
                    diff_pos = [
                        (i, self._ref_seq[i], self._alt_seq[i])
                        for i in range(len(self._ref_seq))
                        if self._ref_seq[i] != self._alt_seq[i]
                    ]
                    if len(diff_pos) == 1:
                        (start, deletion, insertion) = diff_pos[0]
                        variants.append({"start": start + 1, "ins": insertion, "del": deletion})
                        do_delins = False

            if do_delins:
                if self._alt_data.is_frameshift:
                    start = self._alt_data.variant_start_aa - 1
                    while self._ref_seq[start] == self._alt_seq[start]:
                        start += 1
                    insertion = list(self._alt_seq[start:])
                    deletion = list(self._ref_seq[start:])
                    variants.append({"start": start + 1, "ins": insertion, "del": deletion})

                else:  # non-frameshifting delins or dup
                    # get size diff from diff in ref/alt lengths
                    start = self._alt_data.variant_start_aa - 1
                    delta = len(self._alt_seq) - len(self._ref_seq)
>                   while self._ref_seq[start] == self._alt_seq[start]:
E                   IndexError: string index out of range

src/hgvs/utils/altseq_to_hgvsp.py:102: IndexError

Also see here:

The VEP prediction is correct * => ** plus inframe_insertion&stop_retained_variant.

#Uploaded_variation Location Allele Consequence IMPACT SYMBOL Gene Feature_type Feature BIOTYPE EXON INTRON HGVSc HGVSp cDNA_position CDS_position Protein_position Amino_acids Codons Existing_variation DISTANCE STRAND FLAGS SYMBOL_SOURCE HGNC_ID MANE_SELECT MANE_PLUS_CLINICAL TSL APPRIS REFSEQ_MATCH REFSEQ_OFFSET GIVEN_REF USED_REF BAM_EDIT SIFT PolyPhen AF CLIN_SIG SOMATIC PHENO PUBMED MOTIF_NAME MOTIF_POS HIGH_INF_POS MOTIF_SCORE_CHANGE TRANSCRIPTION_FACTORS
. 10:5139789-5139789 GTG inframe_insertion,stop_retained_variant MODERATE AKR1C3 8644 Transcript NM_001253909.2 protein_coding 3/3 - - - 447-448 416-417 139 /* taa/taGTGa - - 1 - EntrezGene - - - - - - - - - - - - - - - - - - - - - -
holtgrewe added a commit to holtgrewe/hgvs that referenced this issue Oct 21, 2023
@holtgrewe
fix: projection issue for stop retained insertion (biocommons#707)
4ae9644
@holtgrewe holtgrewe linked a pull request Oct 21, 2023 that will close this issue
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This issue is stale because it has been open 30 days with no activity. Remove stale label or comment or this will be closed in 7 days.

@github-actions github-actions bot added the stale Issue is stale and subject to automatic closing label Nov 28, 2023
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github-actions bot commented Dec 5, 2023

This issue was closed because it has been stalled for 7 days with no activity.

@github-actions github-actions bot closed this as not planned Won't fix, can't repro, duplicate, stale Dec 5, 2023
@reece reece removed stale Issue is stale and subject to automatic closing closed-by-stale labels Dec 8, 2023
@reece reece reopened this Dec 8, 2023
@jsstevenson jsstevenson added the bug Something isn't working label Dec 30, 2023
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fix: projection issue for stop retained insertion (#707) holtgrewe/hgvs
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@reece @holtgrewe @jsstevenson