PVS1
Insufficient evidence was available to assess PVS1 (loss-of-function mechanism).
PS2
Not assessed: no proband, family-history, or parental-testing data were available to evaluate a de novo occurrence.
PS3
Not assessed: no validated functional assay of this exact variant was available; functional data concern other MBD4 truncations only.
PS4
Not met: no case-control or prevalence study reports this exact variant, and gene-level disease association does not qualify.
PM3
Not met: no source documents this variant in trans with a pathogenic variant, and no homozygotes are observed.
PM6
Not assessed: no de novo occurrence of this variant is documented, and no proband data exist to assess one.
PP1
Not assessed: no family segregation data exist for this variant; segregation of other MBD4 alleles does not apply.
PP3
Not met: SpliceAI max delta 0.06 is below the 0.2 splice-disruption threshold, and missense scores do not apply to a frameshift.
PP4
Not assessed: no proband phenotype or family-history information was available to judge phenotype specificity.
PP5
Not met: no ClinGen expert-panel classification exists; three clinical-laboratory Pathogenic submissions do not trigger PP5.
