ClinVar Miner

Submissions for variant NM_000133.4(F9):c.1235G>A (p.Gly412Glu)

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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 RCV003510979 SCV004363680 pathogenic Hereditary factor IX deficiency disease 2024-02-09 reviewed by expert panel curation The c.1235G>A (NM_000133.4) variant in F9 is a missense variant predicted to cause substitution of Glycine by Glutamate at amino acid 412 (p.Gly412Glu). This variant has been reported in at least 8 probands meeting the hemophilia B phenotype criteria specified by the Coagulation Factor Deficiency VCEP (PS4_VeryStrong; PMID: 10874302, 29296726, 1680287, 8055323, 12588353). At least one patient with this variant meets the VCEP specification for PP4 (PP4_Moderate, MLOF study). This variant is absent from gnomAD v2.1.1 and v3.1.1 (PM2_Supporting). The computational predictor REVEL gives a score of 0.981, which is above the threshold of 0.6, evidence that correlates with impact to F9 function (PP3). In summary, this variant meets the criteria to be classified as Pathogenic for X-linked recessive hemophilia B based on the ACMG/AMP criteria applied, as specified by the ClinGen Coagulation Factor Deficiency VCEP: PS4_VeryStrong, PP4_Moderate, 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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