PVS1
Not met: the intronic +11 variant has SpliceAI max delta 0.005 and lacks evidence of abnormal splicing, NMD, or a protein-truncating consequence.
PS2
Not assessed: no documented proband-parent testing or confirmed de novo event is available for NM_001042492.2:c.4577+11C>G.
PS3
Not assessed: no variant-specific validated functional assay or RNA/protein result demonstrates that c.4577+11C>G disrupts NF1 function or splicing.
PS4
Not assessed: no exact-variant affected-case series or case-control enrichment statistic is available to establish increased NF1 prevalence.
PM2
Not met: gnomAD v4.1 AF is 0.00097426, nearly tenfold above the generic PM2 threshold of 0.0001.
PM3
Not assessed: no affected-proband observation documents a pathogenic NF1 allele in trans with c.4577+11C>G.
PM6
Not assessed: no report identifies NM_001042492.2:c.4577+11C>G as apparently de novo without parental confirmation.
PP1
Not assessed: no affected relatives, informative meioses, or phenotype-consistent familial segregation are documented for this variant.
PP3
Not met: SpliceAI maximum delta 0.005 is below the 0.2 supporting threshold for intronic variants.
PP4
Not assessed: no patient phenotype or exact-variant phenotype correlation is available to demonstrate a highly specific NF1 presentation.
PP5
Not met: exact-variant ClinVar has zero expert-panel submissions and reports laboratory classifications as benign or likely benign.
