The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
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  • See Evidence submitted by expert panel for details.

Variant: NM_000488.4(SERPINC1):c.449A>C (p.Gln150Pro)

CA1251409

654211 (ClinVar)

Gene: SERPINC1
Condition: antithrombin III deficiency
Inheritance Mode: Autosomal dominant inheritance
UUID: 6fdd3bac-395e-4fdd-9e42-2c552b360524
Approved on: 2024-05-09
Published on: 2024-05-09

HGVS expressions

NM_000488.4:c.449A>C
NM_000488.4(SERPINC1):c.449A>C (p.Gln150Pro)
NC_000001.11:g.173911974T>G
CM000663.2:g.173911974T>G
NC_000001.10:g.173881112T>G
CM000663.1:g.173881112T>G
NC_000001.9:g.172147735T>G
NG_012462.1:g.10405A>C
ENST00000367698.4:c.449A>C
ENST00000367698.3:c.449A>C
ENST00000487183.1:n.154A>C
ENST00000617423.4:c.449A>C
NM_000488.3:c.449A>C
NM_001365052.1:c.305A>C
NM_001365052.2:c.305A>C
NM_001386302.1:c.449A>C
NM_001386303.1:c.530A>C
NM_001386304.1:c.449A>C
NM_001386305.1:c.449A>C
NM_001386306.1:c.409-1083A>C
More

Likely Pathogenic

Met criteria codes 4
PM2_Supporting PS4 PP3 PP4

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Thrombosis VCEP
The NM_000488.4:c.449A>C variant in SERPINC1 is a missense variant predicted to cause substitution of Glutamine by Proline at amino acid 150 (p.Gln150Pro). This variant is also known as antithrombin Vienna (Legacy nomenclature: Gln118Pro) in the literature. At least one patient with this variant displayed AT deficiency (type II- HBD) which is highly specific for SERPINC1 (PP4, PMID: 7734360). The computational predictor REVEL gives a score of 0.865, which is above the threshold of 0.6, evidence that correlates with impact to SERPINC1 gene function. The highest population minor allele frequency in gnomAD v2.1.1 is 0.000008791 (1/113750 alleles) in the non-Finnish European population, which is lower than the ClinGen Thrombosis VCEP threshold (<0.00002 ) for PM2_Supporting, meeting this criterion. In summary, this variant meets the criteria to be classified as a pathogenic for antithrombin deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Thrombosis VCEP. (Specifications version 1.0.0; date of approval: 7/17/2023).
Met criteria codes
PM2_Supporting
The highest population minor allele frequency in gnomAD v2.1.1 is 0.000008791 (1/113750 alleles) in the non-Finnish European population, which is lower than the ClinGen Thrombosis VCEP threshold (<0.00002 ) for PM2_Supporting, meeting this criterion.
PS4
Potentially 10 individuals with this variant and AT deficiency would contribute 10 points towards PS4_VeryStrong. To be updated following expert review.
PP3
The computational predictor REVEL gives a score of 0.865, which is above the threshold of 0.6, evidence that correlates with impact to SERPINC1 gene function.
PP4
At least one patient with this variant displayed AT deficiency (type II- HBD) which is highly specific for SERPINC1 (PP4, PMID: 7734360)
Curation History
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