PS1
No evidence was identified showing that a different nucleotide change produces the same amino acid substitution with an established pathogenic interpretation.
PS2
No confirmed de novo occurrence with verified maternity and paternity was identified.
PS3
No published functional study specific to p.(Asn626Asp) was identified that demonstrates a damaging effect using a validated assay.
PS4
Somatic database curation suggests this variant has been observed in cancers, but no germline case-control or affected-versus-control enrichment data were identified for this variant.
PM1
A hotspot signal was suggested, but the reviewed hotspot evidence for codon 626 was marked uncertain and did not confirm that this exact residue is an established mutational hotspot or critical benign-variant-depleted region.
PM3
No evidence was identified showing this variant in trans with a pathogenic variant for a recessive disorder.
PM5
No evidence was identified showing a different pathogenic missense change at the same codon that would support PM5.
PM6
No presumed de novo occurrence without confirmed parentage was identified.
PP1
No segregation data were identified to show co-segregation with disease in affected family members.
PP2
Available evidence shows SF3B1 missense variation can be clinically relevant, but no gene-specific missense-rate framework was identified to support applying PP2 in this case.
PP3
Computational evidence is mixed.
PP4
No phenotype information was provided that would allow assessment of whether the clinical presentation is highly specific for an SF3B1-related disorder.
PP5
No qualifying pathogenic classification from a germline clinical database or other accepted external clinical source was identified for this variant.
