The FBXO31 c.1000G>A (p.Asp334Asn) variant has not been observed in somatic cancers in COSMIC and has been reported in ClinVar with pathogenic and likely pathogenic clinical submissions.
clinvar ↗This variant is absent from gnomAD v2.1 and gnomAD v4.1, so its observed population frequency is 0 and is below the 0.1% threshold used here to support rarity.
gnomad_v2 ↗ gnomad_v4 ↗In a published functional study, fibroblast assays from affected individuals showed reduced cyclin D abundance relative to controls, and the authors interpreted p.Asp334Asn as causing increased cyclin D degradation, supporting a damaging effect on FBXO31 function.
PMID:32989326 ↗Published reports describe recurrent de novo occurrence in three unrelated affected individuals, while computational evidence is mixed: SpliceAI predicts no splice effect with a max delta score of 0.00, REVEL is 0.455, and BayesDel is -0.150532, so in silico data alone do not strongly support either PP3 or BP4.
PMID:32989326 ↗ PMID:33675180 ↗ spliceai ↗
