c.3170G>A (p.Ser1057Asn) is a missense variant in BRCA1 exon 10 (legacy exon 11) located at amino acid position 1057, outside the established clinically important functional domains (RING aa 2-101, coiled-coil aa 1391-1424, BRCT aa 1650-1857).¹ SpliceAI predicts no splicing impact (max delta score 0.00), and BayesDel no-AF score is -0.0291, consistent with a benign computational prediction.² BP1_Strong is met: the variant is a missense substitution outside clinically important functional domains with no predicted splicing impact (SpliceAI ≤0.1). This is the only applicable ACMG/AMP criterion supported by current evidence.³ BRCA1 exon 11 (aa 224-1366), where p.Ser1057Asn resides, has been characterized as a coldspot with zero pathogenic or likely pathogenic missense variants among 1,117 exon 11 missense variants reported to ClinVar.⁴ The variant is present at extremely low frequency in population databases (gnomAD v2.1: 1/250,824 alleles, AF=0.0004%; gnomAD v4.1: 3/1,613,924 alleles, grpmax FAF=6.8e-7), below thresholds for both benign (BS1) and pathogenic (PM2) population criteria.⁵ No functional data, case-control studies, segregation analysis, clinical history likelihood ratios, or variant-specific publications were identified for this variant. It is reported in ClinVar as Uncertain Significance (5 clinical laboratories, single submitter criteria only, no expert panel review).⁶ Under the ENIGMA BRCA1 v1.2 point-based classification system, the evidence totals -4 points (BP1_Strong alone), placing the variant in the Likely Benign range (-6 to -2). However, ENIGMA Table 3 requires multiple evidence types to support Likely Benign when based on a single Strong Benign criterion. With only BP1_Strong met and no additional benign criteria satisfied from independent evidence types, the classification defaults to Uncertain Significance per the ENIGMA adapted ACMG/AMP framework.⁷