Submissions for variant NM_000488.4(SERPINC1):c.1011A>G (p.Gln337=)

gnomAD frequency: 0.48194  dbSNP: rs5878

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Clingen Thrombosis Variant Curation Expert Panel, ClinGen	RCV000292511	SCV004037399	benign	Hereditary antithrombin deficiency	2023-07-25	reviewed by expert panel	curation	The variant is reported at a popmax FAF of 0.7651 and the highest MAF of 0.7792 (78%; 19440/24948 alleles with 7592 homozygotes) in the African/African-American population in gnomAD v2.1.1, meeting criteria for BA1 (MAF >0.002). The variant is reported in 1 individual with normal antithrombin levels. SpliceAI and VarSeak predict no impact on splicing and PhyloP gives a conservation score of 0.028 (<0.1). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for SERPINC1: BA1, BS2_Supporting, BP4, BP7.
PreventionGenetics, part of Exact Sciences	RCV000244198	SCV000304463	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000292511	SCV000351481	benign	Hereditary antithrombin deficiency	2018-01-13	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000292511	SCV000999945	benign	Hereditary antithrombin deficiency	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001706297	SCV001843986	benign	not provided	2018-10-31	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000292511	SCV002054786	benign	Hereditary antithrombin deficiency	2021-07-15	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001706297	SCV005288536	benign	not provided		criteria provided, single submitter	not provided