Submissions for variant NM_000488.4(SERPINC1):c.981A>G (p.Val327=)

gnomAD frequency: 0.48114  dbSNP: rs5877

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Clingen Thrombosis Variant Curation Expert Panel, ClinGen	RCV000392683	SCV004037382	benign	Hereditary antithrombin deficiency	2023-07-25	reviewed by expert panel	curation	The c.981A>G (p.Val327=) variant is reported at an Popmax FAF MAF of 0.7471 (19267/24962 alleles) in the African/African-American population in the genomes in gnomAD v2.1.1 with a total of 26873 homozygotes, meeting BA1 criteria of FAF >= 0.002. The variant has been reported in one heterozygous individual with normal AT activity levels (85%) meeting BS2_Supporting criteria. This synonymous variant is not predicted to impact splicing by SpliceAI and VARSEAK meeting BP4 criteria. 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, BP4, BS2_Supporting.
PreventionGenetics, part of Exact Sciences	RCV000254137	SCV000304465	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000392683	SCV000351483	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	RCV000392683	SCV000999946	benign	Hereditary antithrombin deficiency	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001711654	SCV001941112	benign	not provided	2018-10-31	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000392683	SCV002054787	benign	Hereditary antithrombin deficiency	2021-07-15	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001711654	SCV005288537	benign	not provided		criteria provided, single submitter	not provided