Submissions for variant NM_000488.4(SERPINC1):c.29C>A (p.Thr10Asn)

gnomAD frequency: 0.00029  dbSNP: rs61736655

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Clingen Thrombosis Variant Curation Expert Panel, ClinGen	RCV001101594	SCV005061616	likely benign	Hereditary antithrombin deficiency	2024-02-19	reviewed by expert panel	curation	The c.29C>A (NM_000488.3) variant in SERPINC1 is a missense variant predicted to cause substitution of threonine by asparagine at amino acid 10 (p.Thr10Asn). The highest population minor allele frequency in gnomAD v2.1.1 is 0.0003178 (41/129000 alleles) in the European population, which is higher than the ClinGen SERPINC1 threshold ([>0.0002]) for BS1, and therefore meets this criterion (BS1). The computational predictor REVEL gives a score of 0.141, 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). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for SERPINC1: BS1, BP4
Illumina Laboratory Services, Illumina	RCV001101594	SCV001258218	uncertain significance	Hereditary antithrombin deficiency	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001101594	SCV001645952	likely benign	Hereditary antithrombin deficiency	2024-12-20	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV003480953	SCV004224702	uncertain significance	not provided	2022-08-26	criteria provided, single submitter	clinical testing	BP4