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.1095C>G

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA343772391

Gene: SERPINC1

Condition: antithrombin III deficiency

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: e969f093-b6e9-4944-8519-e89b0379626f

Approved on: 2024-02-19

Published on: 2024-02-19

HGVS expressions

NM_001386306.1:c.1095C>G

NC_000001.11:g.173903973G>C

CM000663.2:g.173903973G>C

NC_000001.10:g.173873111G>C

CM000663.1:g.173873111G>C

NC_000001.9:g.172139734G>C

NG_012462.1:g.18406C>G

ENST00000367698.4:c.1311C>G

ENST00000367698.3:c.1311C>G

ENST00000617423.4:c.696C>G

NM_000488.3:c.1311C>G

NM_001365052.1:c.1167C>G

NM_000488.4:c.1311C>G

NM_001365052.2:c.1167C>G

NM_001386302.1:c.1434C>G

NM_001386303.1:c.1392C>G

NM_001386304.1:c.1290C>G

NM_001386305.1:c.1254C>G

Pathogenic

PP1_Strong PS4 PP3

PM2 BS1

Evidence Links 0

Expert Panel

Thrombosis VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Thrombosis VCEP

The c.1311C>G (NM_000488.3) variant in SERPINC1 is a missense variant predicted to cause substitution of asparagine by lysine at amino acid 437 (p.Asn437Lys). The computational predictor REVEL gives a score of 0.683, which is above the threshold of >0.6 and provides evidence that correlates with impact to SERPINC1 function, meeting criteria for PP3. The variant has been reported in at least 8 probands with AT deficiency in the literature (7.5 points applied PMID 28300866; PMID 24684277; PMID 12755798; PMID 1469094). The variant has been reported to segregate with autosomal dominant hereditary antithrombin deficiency in 7 affected family meioses from 4 families (PP1_strong; PMID: 1469094; PMID: 12755798; PMID: 28300866). 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: PP1_Strong, PS4, PP3.

PP1_Strong

The variant has been reported to segregate with autosomal dominant hereditary antithrombin deficiency in 7 affected family meioses from 4 families (PP1_supporting; PMID: 1469094; PMID: 12755798; PMID: 28300866).

PS4

The variant has been reported in at least 8 probands with AT deficiency in the literature (7.5 points applied PMID 28300866; PMID 24684277; PMID 12755798; PMID 1469094).

PP3

The computational predictor REVEL gives a score of 0.683, which is above the threshold of >0.6 and provides evidence that correlates with impact to SERPINC1 function, meeting criteria for PP3.

PM2

The variant is reported at the highest MAF of 0.00005437 (1/18392 alleles) in the East Asian population in gnomAD v2.1.1, which does not meet criteria for PM2_Supporting (MAF =< 2.0 X 10-5 in gnomAD).

BS1

The variant is reported at the highest MAF of 0.00005437 (1/18392 alleles) in the East Asian population in gnomAD v2.1.1, which does not meet criteria for BS1 (MAF >=0.0002).

Curation History

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