The NM_198253.2:c.3334C>A (p.Leu1112Met) missense variant in TERT is absent from large population databases including gnomAD v2.1, v4.1, and gnomAD-Canada (PM2_supporting).¹ Multiple in silico tools predict a benign or neutral effect: REVEL score 0.155, BayesDel score -0.27587, and SpliceAI max delta 0.00 (BP4_supporting).² This variant has been reported in ClinVar as a Variant of Uncertain Significance by two clinical laboratories (ClinVar ID 816668). No functional studies have been performed on this variant.³ The variant is a missense change at a residue that is not located in a mutational hotspot or well-established critical functional domain, and no alternate pathogenic missense variant at the same codon is known.⁴ Overall, the available evidence includes one supporting pathogenic criterion (PM2) and one supporting benign criterion (BP4), yielding a net classification of Variant of Uncertain Significance under the generic ACMG/AMP 2015 framework.⁵