Classification rationale
1
2
This variant is absent from gnomAD v2.1 and gnomAD v4.1, with an observed allele frequency of 0 in both datasets, which is below the 0.1% rarity threshold used to support PM2 at supporting strength.
gnomad_v2 ↗ gnomad_v4 ↗3
PHF6 loss of function is an established disease mechanism, and this nonsense variant is predicted to truncate the protein from 366 to 334 amino acids; however, because the change lies in the last coding exon and removes only the distal C-terminal portion, PVS1 remains for manual review rather than automatic application.
pvs1_generic_framework ↗4
SpliceAI predicts no significant splice impact for this variant, with a maximum delta score of 0.00.
spliceai ↗
