Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000488.4(SERPINC1):c.624+1G>A

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA343776041

694627 (ClinVar)

Gene: SERPINC1

Condition: antithrombin III deficiency

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: c64f2d9b-c0ab-4ced-9cb1-b108253b4d94

Approved on: 2024-01-25

Published on: 2024-01-25

HGVS expressions

NM_000488.4:c.624+1G>A

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

NC_000001.11:g.173911798C>T

CM000663.2:g.173911798C>T

NC_000001.10:g.173880936C>T

CM000663.1:g.173880936C>T

NC_000001.9:g.172147559C>T

NG_012462.1:g.10581G>A

ENST00000367698.4:c.624+1G>A

ENST00000367698.3:c.624+1G>A

ENST00000487183.1:n.329+1G>A

ENST00000617423.4:c.559+66G>A

NM_000488.3:c.624+1G>A

NM_001365052.1:c.480+1G>A

NM_001365052.2:c.480+1G>A

NM_001386302.1:c.624+1G>A

NM_001386303.1:c.705+1G>A

NM_001386304.1:c.624+1G>A

NM_001386305.1:c.624+1G>A

NM_001386306.1:c.409-907G>A

Likely Pathogenic

PVS1_Strong PM2_Supporting PS4_Supporting

Evidence Links 0

Expert Panel

Thrombosis VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Thrombosis VCEP

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.

PVS1_Strong

The variant occurs within the canonical splice donor site (+1,2) 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.

PM2_Supporting

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.

PS4_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).

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.