ClinVar Miner

Submissions for variant NM_000133.4(F9):c.1325G>C (p.Gly442Ala)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Coagulation Factor Deficiency Variant Curation Expert Panel, Clingen RCV004577668 SCV005061644 likely pathogenic Hereditary factor IX deficiency disease 2024-05-09 reviewed by expert panel curation The c.1325G>C (NM_000133.4) variant in F9 is a missense variant predicted to cause substitution of Glycine by Alanine at amino acid 442 (p.Gly442Ala). This variant has been reported in at least 4 probands meeting the hemophilia B phenotype criteria specified by the Coagulation Factor Deficiency VCEP (PS4_Moderate; PMID: 7937052, poster https://www.postersessiononline.eu/173580348_eu/congresos/WFH2018/aula/-M-P_49_WFH2018.pdf, internal laboratory data). This variant is absent from gnomAD v2.1.1 and v3.1.1 (PM2_Supporting). The computational predictor REVEL gives a score of 0.884, which is above the threshold of 0.6, evidence that correlates with impact to F9 function (PP3). Another missense variant c.1234G>A, p.Gly442Arg in the same codon has been classified as pathogenic for hemophilia B by the ClinGen Coagulation Factor Deficiency VCEP (PM5). In summary, this variant meets the criteria to be classified as Likely Pathogenic for X-linked recessive hemophilia B based on the ACMG/AMP criteria applied, as specified by the ClinGen Coagulation Factor Deficiency VCEP: PS4, PM5, PP3, PM2_Supporting. (ClinGen Coagulation Factor Deficiency Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for F9 Version 1.0.0., Released 10/5/2023)

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