Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV004577671 | SCV005061648 | uncertain significance | Hereditary factor IX deficiency disease | 2024-05-09 | reviewed by expert panel | curation | 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) |