ClinVar Miner

Submissions for variant NM_000488.4(SERPINC1):c.31T>A (p.Ser11Thr)

gnomAD frequency: 0.00001  dbSNP: rs1445653081
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clingen Thrombosis Variant Curation Expert Panel, ClinGen RCV001210419 SCV005367695 uncertain significance Hereditary antithrombin deficiency 2024-07-03 reviewed by expert panel curation The c.31T>A (NM_000488.3) variant in SERPINC1 is a missense variant predicted to cause substitution of serine by threonine at amino acid 11 (p.Ser11Thr). The computational predictor REVEL gives a score of 0.107, which is below the threshold of 0.3, and the splice site predictor Splice AI indicate that the variant has no impact on splicing, which suggests that the variant does not impact SERPINC1 function (BP4). The highest population minor allele frequency in gnomAD v2.1.1 is 0.000008804 (1/113588 alleles) in the European population, which is lower than the ClinGen SERPINC1 threshold ([<0.00002]) for PM2, and therefore meets this criterion (PM2_supporting). In summary, based on the evidence available at this time, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for AT Deficiency for SERPINC1: BP4, PM2_supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV001210419 SCV001381905 uncertain significance Hereditary antithrombin deficiency 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces serine with threonine at codon 11 of the SERPINC1 protein (p.Ser11Thr). The serine residue is weakly conserved and there is a small physicochemical difference between serine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with SERPINC1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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