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

CA1251327

Gene: SERPINC1

Condition: antithrombin III deficiency

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 26402b83-5228-4c66-acc7-bb718a5d6887

HGVS expressions

NM_001386306.1:c.642G>C

NC_000001.11:g.173909847C>G

CM000663.2:g.173909847C>G

NC_000001.10:g.173878985C>G

CM000663.1:g.173878985C>G

NC_000001.9:g.172145608C>G

NG_012462.1:g.12532G>C

ENST00000367698.4:c.858G>C

ENST00000367698.3:c.858G>C

ENST00000487183.1:n.509G>C

ENST00000617423.4:c.559+2017G>C

NM_000488.3:c.858G>C

NM_001365052.1:c.714G>C

NM_000488.4:c.858G>C

NM_001365052.2:c.714G>C

NM_001386302.1:c.981G>C

NM_001386303.1:c.939G>C

NM_001386304.1:c.837G>C

NM_001386305.1:c.801G>C

Uncertain Significance

PM5 PP3

PM2 BS1 PS4

Evidence Links 0

Expert Panel

Thrombosis VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Thrombosis VCEP

The NM_000488.4:c.858G>C variant, which predicts a Gln286His missense change is reported at POPMAX FAF of 0.0001666 in the African/African American population in gnomAD v3.1.2, but does not meet BS1 cut-off of >=0.0002. The variant has a REVEL score of 0.697 and meets PP3 cut-off of >0.6. It is not reported in individuals with AT deficiency in the literature, to the best of our knowledge. It is reported in dbSNP (rs139463995). 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 SERPiNC1: PP3.

PM5

Another variant at the same residue, Gln286Pro, has been evaluated by the Thrombosis VCEP to be a pathogenic. PM5 is met.

PP3

The variant has a REVEL score of 0.697 and meets PP3 cut-off of >0.6.

PM2

gnomAD v4.0 Total PopMax = 0.0001546, which is above the 0.00002 cutoff.

BS1

The c.858G>C (p.Gln286His) variant is reported at POPMAX FAF of 0.0001666 in the African/African American population in gnomAD v3.1.2, but does not meet BS1 cut-off of >=0.0002.

PS4

The Gln286His variant is not reported in individuals with AT deficiency in the literature, to the best of our knowledge. It is reported in dbSNP (rs139463995)

Approved on: 2024-05-09

Published on: 2024-05-09

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