PS1
Not met: the D1598 report includes a D1598N-equivalent assay but does not establish a pathogenic alternative-nucleotide variant producing p.Asp1598Asn.
PS2
Not assessed: no documented proband-parent genotype results establish de novo occurrence of c.4792G>A.
PS4
Not assessed: no germline case-control enrichment or affected-versus-control prevalence estimate is available for NM_006445.3:c.4792G>A.
PM1
Not assessed: no authoritative PRPF8 critical-domain annotation or statistically significant hotspot is available for residue 1598.
PM3
Not assessed: no affected proband, second pathogenic allele, or confirmed trans phase is documented for this PRPF8 variant.
PM5
Not met: D1598 substitutions are reported, but no alternate missense change at residue 1598 is established as pathogenic for the relevant germline disorder.
PM6
Not assessed: no report states that c.4792G>A is apparently de novo without parental testing.
PP1
Not assessed: no affected-relative genotypes or informative meioses are reported for segregation analysis.
PP2
Not assessed: no validated PRPF8 missense constraint or gene-level pathogenic-versus-benign missense distribution is provided.
PP3
Not met: REVEL 0.638 is below the >=0.644 supporting PP3 threshold from the ClinGen SVI calibration.
PP4
Not assessed: no patient-level phenotype or highly specific disease presentation is documented for this exact variant.
PP5
Not met: ClinVar has zero expert-panel submissions, and both exact-variant laboratory assertions are Uncertain significance.
