NM_032043.3:c.1372G>C (p.Glu458Gln) is a missense variant in exon 10 of BRIP1. This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada, consistent with PM2 (supporting).¹ Multiple computational tools predict no deleterious effect: REVEL score 0.334, BayesDel score -0.138785, and SpliceAI max delta 0.01, supporting BP4 (supporting).² No well-established functional studies have been performed for this variant; OncoKB reports unknown oncogenic effect (PS3 and BS3 not met).³ ClinVar classifies this variant as Uncertain significance based on 2 clinical laboratory submissions (PS4, PP5 not met).⁴ No segregation data, de novo observations, case-control studies, or variant-specific publications were identified for this variant. This variant does not qualify as a null variant per ClinGen SVI PVS1 recommendations; PVS1 is not applicable.⁵ The evidence yields PM2 (supporting) and BP4 (supporting), which effectively cancel each other. Based on the ACMG/AMP 2015 framework, this variant is classified as Uncertain significance.⁶