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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  • No CSPEC computed assertion could be determined for this classification!

  • See Evidence submitted by expert panel for details.

Variant: NM_000488.4(SERPINC1):c.624+1G>A

CA343776041

694627 (ClinVar)

Gene: SERPINC1
Condition: antithrombin III deficiency
Inheritance Mode: Autosomal dominant inheritance
UUID: c64f2d9b-c0ab-4ced-9cb1-b108253b4d94
Approved on: 2024-01-25
Published on: 2024-01-25

HGVS expressions

NM_000488.4:c.624+1G>A
NM_000488.4(SERPINC1):c.624+1G>A
NC_000001.11:g.173911798C>T
CM000663.2:g.173911798C>T
NC_000001.10:g.173880936C>T
CM000663.1:g.173880936C>T
NC_000001.9:g.172147559C>T
NG_012462.1:g.10581G>A
ENST00000367698.4:c.624+1G>A
ENST00000367698.3:c.624+1G>A
ENST00000487183.1:n.329+1G>A
ENST00000617423.4:c.559+66G>A
NM_000488.3:c.624+1G>A
NM_001365052.1:c.480+1G>A
NM_001365052.2:c.480+1G>A
NM_001386302.1:c.624+1G>A
NM_001386303.1:c.705+1G>A
NM_001386304.1:c.624+1G>A
NM_001386305.1:c.624+1G>A
NM_001386306.1:c.409-907G>A
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Likely Pathogenic

Met criteria codes 3
PVS1_Strong PM2_Supporting PS4_Supporting

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Thrombosis VCEP
The c.624+1G>A (NM_000488.4) variant in SERPINC1 occurs within the canonical splice donor site (+1) of intron 3. The variant is not predicted to disrupt reading frame, the role of the region is unknown, LoF variants are not common in SERPINC1, the variant is present in transcript NM_000488.4, and is predicted to affect >10% of the protein (15% (71AA in Exon 3/464AA total)) meeting criteria for PVS1_Strong.The variant is absent from gnomAD v2.1.1 and v3.1 with good coverage across both genomes and exomes, meeting criteria for PM2_supporting. This variant has been reported in 1 proband with antithrombin activity level of 55 meeting the SERPINC1-phenotypic criteria (AT level of <0.8 IU/mL) (PS4_Supporting; Alhenc-Gelas et al. 2017. PMID: 28300866). In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for AT Deficiency for SERPINC1: PVS1_Strong, PS4_Supporting, PM2_Supporting.
Met criteria codes
PVS1_Strong
The variant occurs within the canonical splice donor site (+1,2) of intron 3. The variant is not predicted to disrupt reading frame, the role of the region is unknown, LoF variants are not common in SERPINC1, the variant is present in transcript NM_000488.4, and is predicted to affect >10% of the protein (15% (71AA in Exon 3/464AA total)) meeting criteria for PVS1_Strong.
PM2_Supporting
The variant is absent from gnomAD v2.1.1 and v3.1 with good coverage across both genomes and exomes, meeting criteria for PM2_supporting.
PS4_Supporting
This variant has been reported in 1 proband with antithrombin activity level of 55 meeting the SERPINC1-phenotypic criteria (AT level of <0.8 IU/mL) (PS4_Supporting; Alhenc-Gelas et al. 2017. PMID: 28300866).
Curation History
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