PS1
No pathogenic or likely pathogenic variant producing the same amino acid substitution was identified in the available evidence, so PS1 was not applied.
PS2
No confirmed de novo occurrence data with verified maternity and paternity were identified, so PS2 was not assessed.
PS3
No well-established functional studies demonstrating a damaging effect of this specific variant were identified, so PS3 was not applied.
PS4
No case-control or enrichment data showing that this variant is more frequent in affected individuals than in controls were identified, so PS4 was not applied.
PM1
This variant has not been identified in a statistically significant hotspot or other established critical functional region without benign variation in the available evidence, so PM1 is not met.
PM3
No evidence was identified showing this variant in trans with a pathogenic variant for a recessive disorder, so PM3 was not assessed.
PM5
No pathogenic missense variant at the same codon was identified in the available evidence, so PM5 was not applied.
PM6
No assumed de novo data without confirmed parentage were identified, so PM6 was not assessed.
PP1
No segregation data were identified to show cosegregation with disease in affected family members, so PP1 was not applied.
PP2
Available evidence does not establish that missense variation is a common disease mechanism for EPCAM, so PP2 was not applied.
PP3
SpliceAI predicts no significant splice impact for this variant (max delta score 0.03), and no validated multi-tool computational framework supporting a damaging missense effect was identified in the available evidence, so PP3 was not applied.
PP4
No phenotype or tumor profile data specific enough to support a highly specific EPCAM-related presentation were identified, so PP4 was not applied.
PP5
ClinVar reports this variant as uncertain significance with no assertion criteria provided, which does not support a pathogenic classification by a reputable source, so PP5 is not met.
