NM_000314.8:c.165-7T>C is an intronic variant in PTEN located at position -7 of the intron 2 splice acceptor region.

This variant is present in gnomAD v4.1 at a grpmax filtering allele frequency of 0.006% (11/1,587,106 alleles), which falls within the PTEN VCEP BS1_Strong range (0.0043%-0.056%), indicating the variant is observed at a population frequency greater than expected for a highly penetrant autosomal dominant disorder.

The variant is classified as Likely benign in ClinVar (VCV000412808) by 5 clinical laboratories, consistent with the population frequency evidence.

SpliceAI predicts no significant splicing impact (max delta score = 0.02), which falls within the benign range for computational splice prediction but is not sufficient alone to apply BP4 under the PTEN VCEP without VarSeak concordance.

No pathogenic computational predictions, functional assay data, segregation evidence, de novo observations, or case-level phenotype data were identified to support pathogenicity for this variant.

The variant does not meet PM2 under PTEN VCEP rules because the South Asian subpopulation frequency (0.0111%) exceeds the VCEP subpopulation threshold of 0.002%.