ClinVar Miner

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

dbSNP: rs121909563
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Total submissions: 4
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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

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