1-173904013-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PP3PM1PM2_SupportingPS4_Supporting
This summary comes from the ClinGen Evidence Repository: The c.1271G>A variant in SERPINC1 is a missense variant predicted to cause substitution of glycine by aspartic acid at amino acid 424 (p.Gly424Asp). This variant has been reported in one family meeting an antithrombin activity level of < 0.8 IU/mL and a family history of reported abnormal antithrombin levels (PS4_Supporting; PMID:1547341).The computational predictor REVEL gives a score of 0.635, which is above the threshold of 0.6, evidence that correlates with impact to SERPINC1 function (PP3). This variant is absent from gnomAD v4.1.0 (PM2_Supporting).In summary, this variant meets the criteria to be classified as uncertain significance due to insufficient evidence for autosomal dominant hereditary antithrombin deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Thrombosis VCEP: PP3, PM2_Supporting, PS4_Supporting. LINK:https://erepo.genome.network/evrepo/ui/classification/CA210785/MONDO:0013144/084
Frequency
Consequence
ENST00000367698.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SERPINC1 | NM_000488.4 | c.1271G>A | p.Gly424Asp | missense_variant | 7/7 | ENST00000367698.4 | NP_000479.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SERPINC1 | ENST00000367698.4 | c.1271G>A | p.Gly424Asp | missense_variant | 7/7 | 1 | NM_000488.4 | ENSP00000356671 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary antithrombin deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 1992 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at