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_001313913.2:c.1190G>T

CA414447224

Gene: F9

Condition: hemophilia B

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: a1984bb7-6cd4-4701-9596-276a255f89c4

Approved on: 2024-05-09

Published on: 2024-05-09

HGVS expressions

NM_001313913.2:c.1190G>T

NC_000023.11:g.139561989G>T

CM000685.2:g.139561989G>T

NC_000023.10:g.138644148G>T

CM000685.1:g.138644148G>T

NC_000023.9:g.138471814G>T

NG_007994.1:g.36254G>T

ENST00000218099.7:c.1304G>T

ENST00000643157.1:n.1723+248G>T

ENST00000218099.6:c.1304G>T

ENST00000394090.2:c.1190G>T

NM_000133.3:c.1304G>T

NM_001313913.1:c.1190G>T

NM_000133.4:c.1304G>T

Uncertain Significance

PM2_Supporting PP3 PM5 PS4_Supporting

Evidence Links 0

Expert Panel

Coagulation Factor Deficiency VCEP

Criteria Specification Information

Criteria Specification: ClinGen Coagulation Factor Deficiency Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for F9 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Coagulation Factor Deficiency VCEP

The NM_000133.4:c.1304G> variant in F9 is a missense variant predicted to cause substitution of Cys by Phe at amino acid 435 (p.Cys435Phe). This variant has been reported in 1 proband meeting F9 phenotype criteria (PS4_Supporting; PMID: 19686262). The computational predictor REVEL gives a score of 0.965, which is above the threshold of 0.6, evidence that correlates with impact to F9 function (PP3). Another missense variant c.1304G>A (p.Cys435Tyr) in the same codon has been classified as pathogenic for hemophilia B by the ClinGen Coagulation Factor Deficiency VCEP (PM5). This variant is absent from gnomAD v2, v3 and v4. In summary, this variant meets the criteria to be classified as a variant of uncertain significance for hemophilia B based on the ACMG/AMP criteria applied, as specified by the ClinGen Coagulation Factor Deficiency VCEP: PS4_Supporting, PM2_Supporting, PP3, PM5. (Version 1.0.0, 10/05/2023)

PM2_Supporting

This c.1304G>T (p.Cys435Phe) variant is absent from gnomAD v2, v3 and v4.

PP3

The computational predictor REVEL gives a score of 0.965, which is above the threshold of 0.6, evidence that correlates with impact to F9 function (PP3).

PM5

Another missense variant c.1304G>A (p.Cys435Tyr) in the same codon has been classified as pathogenic for hemophilia B by the ClinGen Coagulation Factor Deficiency VCEP (PM5).

PS4_Supporting

This variant has been reported in 1 proband meeting F9 phenotype criteria (PS4_Supporting; PMID: 19686262)

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