ClinVar Miner

Submissions for variant NM_000488.4(SERPINC1):c.624+1G>A

dbSNP: rs1572090079
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clingen Thrombosis Variant Curation Expert Panel, ClinGen RCV000856668 SCV005061629 likely pathogenic Hereditary antithrombin deficiency 2024-01-25 reviewed by expert panel curation The c.624+1G>A (NM_000488.4) variant in SERPINC1 occurs within the canonical splice donor site (+1) of intron 3. The variant is not predicted to disrupt reading frame, the role of the region is unknown, LoF variants are not common in SERPINC1, the variant is present in transcript NM_000488.4, and is predicted to affect >10% of the protein (15% (71AA in Exon 3/464AA total)) meeting criteria for PVS1_Strong.The variant is absent from gnomAD v2.1.1 and v3.1 with good coverage across both genomes and exomes, meeting criteria for PM2_supporting. This variant has been reported in 1 proband with antithrombin activity level of 55 meeting the SERPINC1-phenotypic criteria (AT level of <0.8 IU/mL) (PS4_Supporting; Alhenc-Gelas et al. 2017. PMID: 28300866). 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 AT Deficiency for SERPINC1: PVS1_Strong, PS4_Supporting, PM2_Supporting.
Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology RCV000856668 SCV000998941 pathogenic Hereditary antithrombin deficiency 2019-11-08 criteria provided, single submitter clinical testing The variant causes alteration of a wild type donor splice-site. The c.624+1G>A variant is not present in publicly available databases like 1000 Genomes, Exome Variant Server (EVS), Exome Aggregation Consortium (ExAC), Genome Aggregation Database (gnomAD) and dbSNP. The variant is also not present in our in-house exome database. The variant was also not reported to OMIM, ClinVar and Human Genome Mutation Database (HGMD) in any other affected individuals. However a different base change (c.624+1G>T) in the same position was reported in HGMD (ID: CS126235) in similarly affected individuals . In-silico pathogenicity prediction programs like Mutation Taster2, CADD etc. predicted this variant as likely disease causing.

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