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_001386306.1:c.1096A>G

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA343772388

Gene: SERPINC1

Condition: antithrombin III deficiency

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 0e26b3da-0730-4e5c-a373-4b7ca7a3652f

Approved on: 2024-02-19

Published on: 2024-02-19

HGVS expressions

NM_001386306.1:c.1096A>G

NC_000001.11:g.173903972T>C

CM000663.2:g.173903972T>C

NC_000001.10:g.173873110T>C

CM000663.1:g.173873110T>C

NC_000001.9:g.172139733T>C

NG_012462.1:g.18407A>G

ENST00000367698.4:c.1312A>G

ENST00000367698.3:c.1312A>G

ENST00000617423.4:c.697A>G

NM_000488.3:c.1312A>G

NM_001365052.1:c.1168A>G

NM_000488.4:c.1312A>G

NM_001365052.2:c.1168A>G

NM_001386302.1:c.1435A>G

NM_001386303.1:c.1393A>G

NM_001386304.1:c.1291A>G

NM_001386305.1:c.1255A>G

Uncertain Significance

PS4_Supporting PM2_Supporting PP3

Evidence Links 0

Expert Panel

Thrombosis VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Thrombosis VCEP

The c.1312A>G (NM_000488.3) variant in SERPINC1 is a missense variant predicted to cause substitution of arginine by glycine at amino acid 438 (p.Arg438Gly). The variant is absent from gnomAD v2.1.1, v3.1, v4.0.0 with good coverage across both genomes and exomes, meeting criteria for PM2_supporting. The computational predictor REVEL gives a score of 0.752, which is above the threshold of >0.6 and provides evidence that correlates with impact to SERPINC1 function, meeting criteria for PP3. This variant has been reported in a single patient with an antithrombin activity level of 45-53% meeting the SERPINC1-phenotypic criteria (AT level of <0.8 IU/mL) (PS4_Supporting). In summary, based on the evidence available at this time, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for AT Deficiency for SERPINC1: PP3, PM2_Supporting, PS4_ Supporting.

PS4_Supporting

This variant has been reported in a 38-y.o. female proband with antithrombin activity level of 45-53% meeting the SERPINC1-phenotypic criteria (AT level of <0.8 IU/mL).

PM2_Supporting

The variant is absent from gnomAD v2.1.1, v3.1, v4.0.0 with good coverage across both genomes and exomes, meeting criteria for PM2_supporting.

PP3

The computational predictor REVEL gives a score of 0.752, which is above the threshold of >0.6 and provides evidence that correlates with impact to SERPINC1 function (PP3).

Curation History

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