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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000488.4(SERPINC1):c.1271G>A (p.Gly424Asp)

CA210785

18033 (ClinVar)

Gene: SERPINC1
Condition: antithrombin III deficiency
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: e778a9b4-7095-4fb1-a108-f6641ca4fee3
Approved on: 2024-12-20
Published on: 2024-12-20

HGVS expressions

NM_000488.4:c.1271G>A
NM_000488.4(SERPINC1):c.1271G>A (p.Gly424Asp)
NC_000001.11:g.173904013C>T
CM000663.2:g.173904013C>T
NC_000001.10:g.173873151C>T
CM000663.1:g.173873151C>T
NC_000001.9:g.172139774C>T
NG_012462.1:g.18366G>A
ENST00000367698.4:c.1271G>A
ENST00000367698.3:c.1271G>A
ENST00000617423.4:c.656G>A
NM_000488.3:c.1271G>A
NM_001365052.1:c.1127G>A
NM_001365052.2:c.1127G>A
NM_001386302.1:c.1394G>A
NM_001386303.1:c.1352G>A
NM_001386304.1:c.1250G>A
NM_001386305.1:c.1214G>A
NM_001386306.1:c.1055G>A
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Uncertain Significance

Met criteria codes 4
PM1 PM2_Supporting PS4_Supporting PP3

Evidence Links 0

Expert Panel

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.1271G>A variant in SERPINC1 is a missense variant predicted to cause substitution of glycine by aspartic acid at amino acid 424 (p.Gly424Asp). This variant has been reported in one family meeting an antithrombin activity level of < 0.8 IU/mL and a family history of reported abnormal antithrombin levels (PS4_Supporting; PMID:1547341). The computational predictor REVEL gives a score of 0.635, which is above the threshold of 0.6, evidence that correlates with impact to SERPINC1 function (PP3). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). In summary, this variant meets the criteria to be classified as uncertain significance due to insufficient evidence for autosomal dominant hereditary antithrombin deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Thrombosis VCEP: PP3, PM2_Supporting, PS4_Supporting.
Met criteria codes
PM1
This variant resides within a region, Gly424, of SERPINC1 that is a critical functional domain as affirmd by the ClinGen Thrombosis VCEP (PM1).
PM2_Supporting
This variant is absent from gnomAD v4.1.0 (PM2_Supporting).
PS4_Supporting
This variant has been reported in one family meeting an antithrombin activity level of < 0.8 IU/mL and a family history of reported abnormal antithrombin levels (PS4_Supporting; PMID:1547341).
PP3
The computational predictor REVEL gives a score of 0.635, which is above the threshold of 0.6, evidence that correlates with impact to SERPINC1 function (PP3).
Curation History
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