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]

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Variant: NM_000488.3(SERPINC1):c.553A>G (p.Thr185Ala)

CA1251401

529742 (ClinVar)

Gene: SERPINC1

Condition: antithrombin III deficiency

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 7c0af6f2-faa1-4ffd-8bf0-ca35b861aaaf

Approved on: 2023-07-25

Published on: 2023-09-29

HGVS expressions

NM_000488.3:c.553A>G

NM_000488.3(SERPINC1):c.553A>G (p.Thr185Ala)

NC_000001.11:g.173911870T>C

CM000663.2:g.173911870T>C

NC_000001.10:g.173881008T>C

CM000663.1:g.173881008T>C

NC_000001.9:g.172147631T>C

NG_012462.1:g.10509A>G

ENST00000367698.4:c.553A>G

ENST00000367698.3:c.553A>G

ENST00000487183.1:n.258A>G

ENST00000617423.4:c.553A>G

NM_001365052.1:c.409A>G

NM_000488.4:c.553A>G

NM_001365052.2:c.409A>G

NM_001386302.1:c.553A>G

NM_001386303.1:c.634A>G

NM_001386304.1:c.553A>G

NM_001386305.1:c.553A>G

NM_001386306.1:c.409-979A>G

NM_000488.4(SERPINC1):c.553A>G (p.Thr185Ala)

Likely Benign

BS1 BP4

Evidence Links 0

Expert Panel

Thrombosis VCEP

Criteria Specification Information

Criteria Specification: ClinGen Thrombosis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for SERPINC1 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Thrombosis VCEP

The c.553A>G (NM_000488.3) variant in SERPINC1 is a missense variant predicted to cause substitution of threonine by alanine at amino acid 185 (p.Thr185Ala). The highest population minor allele frequency in gnomAD v2.1.1 is 0.001796 (55/30616 alleles) in the South Asian population, which is higher than the ClinGen SERPINC1 threshold ([>0.0002]) for BS1, and therefore meets this criterion (BS1). The computational predictor REVEL gives a score of 0.168, which is below the threshold of 0.3, and the splice site predictors VarSEAK and Splice AI indicated that the variant has no impact on splicing, which suggests that the variant does not impact SERPINC1 function (BP4). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for SERPINC1: BS1, BS4

BS1

The highest population minor allele frequency in gnomAD v2.1.1 is 0.001796 (55/30616 alleles) in the South Asian population, which is higher than the ClinGen SERPINC1 threshold ([>0.0002]) for BS1, and therefore meets this criterion (BS1).

BP4

The computational predictor REVEL gives a score of 0.168, which is below the threshold of 0.3, and the splice site predictors VarSEAK and Splice AI indicated that the variant has no impact on splicing, suggests that the variant does not impact SERPINC1 function (BP4).

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