Submissions for variant NM_000488.4(SERPINC1):c.482G>A (p.Arg161Gln)

dbSNP: rs121909563

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Clingen Thrombosis Variant Curation Expert Panel, ClinGen	RCV000019646	SCV005367710	pathogenic	Hereditary antithrombin deficiency	2024-07-03	reviewed by expert panel	curation	The c.482G>A (NM_000488.3) variant in SERPINC1 is a missense variant predicted to cause substitution of arginine by glutamine at amino acid 161 (p.Arg161Gln also known as ATIII Geneva). The highest population minor allele frequency in gnomAD v2.1.1 is 0.000008790 (1/113762 alleles) in the European population, which is lower than the ClinGen SERPINC1 threshold ([<0.00002]) for PM2, and therefore meets this criterion (PM2_supporting). The computational predictor REVEL gives a score of 0.691, which is above the threshold of >0.6 and provides evidence that correlates with impact to SERPINC1 function, meeting criteria for PP3. The variant has been reported in at least 9 probands with AT deficiency in the literature (9 points applied PMID 28300866, PMID 2229057, PMID 3603409). In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for SERPINC1: PM2_supporting, PP3, PS4_very strong.
OMIM	RCV000019646	SCV000039944	pathogenic	Hereditary antithrombin deficiency	1990-11-05	no assertion criteria provided	literature only
CSER _CC_NCGL, University of Washington	RCV000019646	SCV000190630	uncertain significance	Hereditary antithrombin deficiency	2014-06-01	no assertion criteria provided	research
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV000019646	SCV002515493	pathogenic	Hereditary antithrombin deficiency		no assertion criteria provided	clinical testing