NM_001012338.2:c.428C>T is a missense variant in NTRK3 resulting in a serine to leucine substitution at codon 143 (p.Ser143Leu). This variant is present at extremely low frequency in gnomAD population databases (v2.1 AF=7.96×10⁻⁶, 2/251,180 alleles; v4.1 AF=4.96×10⁻⁶, 8/1,613,870 alleles; no homozygotes; grpmax FAF=2.93×10⁻⁶), meeting PM2 at supporting strength.¹ The variant is absent from ClinVar and has not been reported in the germline literature. It is also absent from COSMIC (somatic cancer database) and OncoKB assigns an Unknown Oncogenic Effect classification.² In silico predictors are equivocal: REVEL score is 0.491 (borderline, below the 0.5 damaging threshold), BayesDel is 0.215, and SpliceAI predicts no splicing impact (max delta 0.03). Neither PP3 nor BP4 is met.³ No functional studies, segregation data, de novo observations, or case-control data are available for this variant. The residue Ser143 is not located in a known mutational hotspot. No CSPEC or VCEP framework exists for NTRK3. Applying generic ACMG/AMP 2015 rules, the only applicable criterion is PM2 (supporting). This is insufficient to classify the variant as likely pathogenic or likely benign.⁴ Overall, NM_001012338.2:c.428C>T is classified as a Variant of Uncertain Significance (VUS) based on a single supporting pathogenic criterion (PM2) and no applicable benign criteria.