Dominguez, M.; Reddin, I. G.; Gibson, J.; Rudraraju, M.; Veal, K.; Kipps, C.; Williams, A.; Ennis, S.

Motivation: Translational interpretation of somatic variants from targeted oncology panels is hampered by inconsistent transcript prioritisation and by the need for reproducible pipelines that natively integrate OncoKB-derived evidence for research purposes. Results: We present SMART (Somatic Mutation Annotation and Reporting Tool), a Dockerised pipeline that embeds OncoKB API-derived annotations, including therapeutic (L1-4), resistance (R1-R3), diagnostic (Dx1-3), prognostic (Px1-3) and FDA levels, directly into a VCF-based workflow. SMART combines this with VEP, CIViC, Cancer Hotspots, ClinVar, SpliceAI, REVEL, LOEUF and gnomAD, applies a unified three-tier transcript prioritisation (whitelist > MANE Select > VEP fallback), and produces three-tiered outputs for computational, bioinformatic and research interpretation. Validation against reference APIs showed full concordance across 804 field-level checks. Availability and Implementation: Source code and Docker image are freely available at https://github.com/WeTGI-colab/SMART under the MIT License. SMART is provided for research use only; use of SMART outputs for patient specific clinical reports, clinical decision-making, or other patient-facing purposes requires appropriate governance and all required third-party licensing, including any OncoKB licence required for patient report generation.