PVS1
Not met: c.505-4A>G is a non-canonical intronic substitution four bases from the exon boundary, not a null variant, with no splice prediction or RNA evidence of an aberrant transcript.
PS2
Not assessed: zero probands and zero parental genotypes exist in the case record, so confirmed de novo occurrence cannot be established.
PS3
Not met: no RNA or enzyme-activity assay of c.505-4A>G exists, and none of the 13 usable ClinVar submissions reports functional evidence.
PS4
Not met: no case-control data exist and gnomAD grpmax FAF 0.0167 with 8 homozygotes is incompatible with the OR > 5.0 enrichment PS4 requires.
PM1
Not met: c.505-4A>G is intronic with no amino-acid change, no MUTYH domain table exists, and no hotspot annotation places it in a functional domain.
PM2
Not met: gnomAD v4.1 total allele frequency 0.09% (1454 alleles; grpmax FAF 1.67%) far exceeds the 0.01% supporting threshold.
PM3
Not assessed: no affected proband reported with c.505-4A>G in trans with a pathogenic MUTYH allele; only population data (gnomAD v4.1: 8 homozygotes, 0.09% AF) are available.
PM6
Not assessed: no proband and no parental genotypes are available in the case, so an assumed de novo occurrence cannot be established.
PP1
Not assessed: no pedigree, affected relatives, or countable meioses exist in the case, so co-segregation cannot be evaluated.
PP3
Not met: SpliceAI max delta 0.024 is below the 0.2 supporting PP3 threshold for this intronic acceptor-region variant.
PP4
Not assessed: no proband phenotype or family history exists in this variant-level case, and MUTYH adenomatous polyposis is not specific to a single genetic etiology.
PP5
Not met: the exact-variant ClinVar record has zero expert-panel submissions and a benign consensus, so no expert-panel pathogenic assertion exists to trigger PP5.
