Evidence Repository
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_000488.4(SERPINC1):c.223G>A (p.Ala75Thr)

CA343777896

2267274 (ClinVar)

Gene: SERPINC1
Condition: antithrombin III deficiency
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 722c0c28-9a10-4a86-9ce0-d548383627c2
Approved on: 2024-07-03
Published on: 2024-07-03

HGVS expressions

NM_000488.4:c.223G>A
NM_000488.4(SERPINC1):c.223G>A (p.Ala75Thr)
NC_000001.11:g.173914738C>T
CM000663.2:g.173914738C>T
NC_000001.10:g.173883876C>T
CM000663.1:g.173883876C>T
NC_000001.9:g.172150499C>T
NG_012462.1:g.7641G>A
ENST00000367698.4:c.223G>A
ENST00000367698.3:c.223G>A
ENST00000494024.1:n.449G>A
ENST00000617423.4:c.223G>A
NM_000488.3:c.223G>A
NM_001365052.1:c.79G>A
NM_001365052.2:c.79G>A
NM_001386302.1:c.223G>A
NM_001386303.1:c.304G>A
NM_001386304.1:c.223G>A
NM_001386305.1:c.223G>A
NM_001386306.1:c.223G>A

Uncertain Significance

Met criteria codes 2
BP4 PM2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Thrombosis VCEP
The c.223G>A (NM_000488.3) variant in SERPINC1 is a missense variant predicted to cause substitution of alanine by threonine at amino acid 75 (p.Ala75Thr). The highest population minor allele frequency in gnomAD v3.1.2 is 0.00001470 (1/68040 alleles) in the European population, which is lower than the ClinGen SERPINC1 threshold ([<0.00002]) for PM2, and therefore meets this criterion (PM2_supporting). The computational predictor REVEL gives a score of 0.215, which is below the threshold of 0.3, and the splice site predictor Splice AI indicate that the variant has no impact on splicing, which suggests that the variant does not impact SERPINC1 function (BP4). 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 AT Deficiency for SERPINC1: BP4, PM2_supporting.
Met criteria codes
BP4
The computational predictor REVEL gives a score of 0.215, which is below the threshold of 0.3, and the splice site predictor Splice AI indicate that the variant has no impact on splicing, which suggests that the variant does not impact SERPINC1 function (BP4).
PM2
The highest population minor allele frequency in gnomAD v3.1.2 is 0.00001470 (1/68040 alleles) in the European population, which is lower than the ClinGen SERPINC1 threshold ([<0.00002]) for PM2, and therefore meets this criterion (PM2_supporting).
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