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.1011A>G (p.Gln337=)

CA1251296

256247 (ClinVar)

Gene: SERPINC1

Condition: antithrombin III deficiency

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: ab43748f-05bd-462b-97f8-fa88f89e47a5

Approved on: 2023-07-25

Published on: 2023-09-29

HGVS expressions

NM_000488.3:c.1011A>G

NM_000488.3(SERPINC1):c.1011A>G (p.Gln337=)

NC_000001.11:g.173909694T>C

CM000663.2:g.173909694T>C

NC_000001.10:g.173878832T>C

CM000663.1:g.173878832T>C

NC_000001.9:g.172145455T>C

NG_012462.1:g.12685A>G

ENST00000367698.4:c.1011A>G

ENST00000367698.3:c.1011A>G

ENST00000617423.4:c.559+2170A>G

NM_001365052.1:c.867A>G

NM_000488.4:c.1011A>G

NM_001365052.2:c.867A>G

NM_001386302.1:c.1134A>G

NM_001386303.1:c.1092A>G

NM_001386304.1:c.990A>G

NM_001386305.1:c.954A>G

NM_001386306.1:c.795A>G

NM_000488.4(SERPINC1):c.1011A>G (p.Gln337=)

Benign

BP7 BP4 BA1 BS2_Supporting

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 variant is reported at a popmax FAF of 0.7651 and the highest MAF of 0.7792 (78%; 19440/24948 alleles with 7592 homozygotes) in the African/African-American population in gnomAD v2.1.1, meeting criteria for BA1 (MAF >0.002). The variant is reported in 1 individual with normal antithrombin levels. SpliceAI and VarSeak predict no impact on splicing and PhyloP gives a conservation score of 0.028 (<0.1). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for SERPINC1: BA1, BS2_Supporting, BP4, BP7.

BP7

SpliceAI and VarSeak predict no impact on splicing and PhyloP gives a conservation score of 0.028 (<0.1). PhastCons prediction gives a score of 0.047. BP7 is met.

BP4

SpliceAI and VarSeak predict no impact on splicing, meeting criteria for BP4

BA1

The variant is reported at a popmax FAF of 0.7651 and the highest MAF of 0.7792 (78%; 19440/24948 alleles with 7592 homozygotes) in the African/African-American population in gnomAD v2.1.1.

BS2_Supporting

The variant is reported in 2 individuals from internal laboratory data. One of them is noted to have unprovoked PE at age 49y and antithrombin activity of 99%. No phenotype information is available for the other individual. BS2_Supporting is applied based on 1 heterozygote with normal antithrombin levels.

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