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]

Link to SEPIO compliant JSON-LD document

Variant: NM_001386306.1:c.562A>T

CA343774795

Gene: SERPINC1

Condition: antithrombin III deficiency

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 6e882c31-d179-4801-8046-1d96d83aee63

Approved on: 2023-09-21

Published on: 2023-09-29

HGVS expressions

NM_001386306.1:c.562A>T

NC_000001.11:g.173909927T>A

CM000663.2:g.173909927T>A

NC_000001.10:g.173879065T>A

CM000663.1:g.173879065T>A

NC_000001.9:g.172145688T>A

NG_012462.1:g.12452A>T

ENST00000367698.4:c.778A>T

ENST00000367698.3:c.778A>T

ENST00000487183.1:n.429A>T

ENST00000617423.4:c.559+1937A>T

NM_000488.3:c.778A>T

NM_001365052.1:c.634A>T

NM_000488.4:c.778A>T

NM_001365052.2:c.634A>T

NM_001386302.1:c.901A>T

NM_001386303.1:c.859A>T

NM_001386304.1:c.757A>T

NM_001386305.1:c.763-42A>T

Pathogenic

PM2_Supporting PS4_Supporting PVS1

Evidence Links 0

Expert Panel

Thrombosis VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Thrombosis VCEP

The c.778A>T, p.Lys260* (NM_000488.3) in SERPINC1 is a nonsense variant predicted to cause a premature stop codon at codon 260 in biologically-relevant exon 5/7 that leads to nonsense mediated decay (PVS1). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant has been reported in 1 proband with antithrombin activity level of 48 meeting the SERPINC1-phenotypic criteria (AT level of <0.8 IU/mL, no repeat testing) (PS4_Supporting; Internal lab contributors). In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for SERPINC1: PVS1, PM2_Supporting, PS4_Supporting.

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_Supporting).

PS4_Supporting

This variant has been reported in 1 proband with antithrombin activity level of 48 meeting the SERPINC1-phenotypic criteria (AT level of <0.8 IU/mL) (PS4_Supporting; Internal lab contributors)

PVS1

The c.778A>T (p.Lys260*) (NM_000488.3) variant in SERPINC1 is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 5/7 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1).

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