PS1
No evidence was identified that a different nucleotide change producing the same amino acid substitution, p.(Ile391Val), has already been established as pathogenic or likely pathogenic.
PS2
No confirmed de novo occurrence with established maternity and paternity was identified for this variant.
PS3
No well-established functional study showing a damaging effect of this specific variant was identified.
PS4
This variant is reported in ClinVar, but available evidence does not provide exact case counts, case-control enrichment, or a statistically increased prevalence in affected individuals compared with controls.
PM1
This variant does not lie in a statistically significant hotspot, and no evidence was identified that codon 391 is a well-established critical functional region without benign variation.
PM3
No evidence was identified that this variant was observed in trans with a pathogenic variant in a recessive disease context.
PM5
No evidence was identified that another missense change at codon 391 has been established as pathogenic or likely pathogenic.
PM6
No presumed de novo occurrence was identified for this variant.
PP1
No segregation data were identified for this variant in affected relatives.
PP2
Available evidence does not establish that BRIP1 is a gene in which pathogenic missense variation is a common mechanism and benign missense variation is uncommon for this specific ACMG criterion.
PP3
Available computational evidence does not support a damaging effect.
PP4
No highly specific phenotype or family history attributable to this exact variant was identified.
PP5
ClinVar lists this variant as uncertain significance with single-submitter review status, which does not provide a qualifying pathogenic reputable-source assertion for PP5.
