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.981A>G (p.Val327=)

CA1251300

256248 (ClinVar)

Gene: SERPINC1

Condition: antithrombin III deficiency

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 42201df9-3651-45a2-957b-3ab904e1abed

HGVS expressions

NM_000488.3:c.981A>G

NM_000488.3(SERPINC1):c.981A>G (p.Val327=)

NC_000001.11:g.173909724T>C

CM000663.2:g.173909724T>C

NC_000001.10:g.173878862T>C

CM000663.1:g.173878862T>C

NC_000001.9:g.172145485T>C

NG_012462.1:g.12655A>G

ENST00000367698.4:c.981A>G

ENST00000367698.3:c.981A>G

ENST00000617423.4:c.559+2140A>G

NM_001365052.1:c.837A>G

NM_000488.4:c.981A>G

NM_001365052.2:c.837A>G

NM_001386302.1:c.1104A>G

NM_001386303.1:c.1062A>G

NM_001386304.1:c.960A>G

NM_001386305.1:c.924A>G

NM_001386306.1:c.765A>G

NM_000488.4(SERPINC1):c.981A>G (p.Val327=)

Benign

BS2_Supporting BA1 BP4

BP7

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.981A>G (p.Val327=) variant is reported at an Popmax FAF MAF of 0.7471 (19267/24962 alleles) in the African/African-American population in the genomes in gnomAD v2.1.1 with a total of 26873 homozygotes, meeting BA1 criteria of FAF >= 0.002. The variant has been reported in one heterozygous individual with normal AT activity levels (85%) meeting BS2_Supporting criteria. This synonymous variant is not predicted to impact splicing by SpliceAI and VARSEAK meeting BP4 criteria. 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, BP4, BS2_Supporting.

BS2_Supporting

The variant has been reported in one heterozygous individual with normal AT activity levels (85%)

BA1

BP4

SpliceAI predicts a donor loss at 3bp downstream with a delta score of 0.14 and the creation of a cryptic donor gain 21bp upstream with a score of 0.03. The scores are low and VARSEAK predicts no splicing impact.

BP7

The variant is not predicted to cause a splicing impact, but the nucleotide is weakly/moderately conserved with a PhyloP score of 1.8 and a PhastCons score of ~1. BP7 is not met.

Approved on: 2023-07-25

Published on: 2023-09-29

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