CYT-low metastatic melanomas were associated with non-silent mutations in GALNTL5, RGPD4, DNAJC5B, DEFA3, IRF2, COL2A1, VEGFC, WFDC11, PROL1, CD80, ADAM18, APOBEC3H and CSHL1; whereas CYT-high metastatic skin tumors were significantly mutated in PPP6C, DSG1, DEFB112, SPATA16, STARD6, RARRES2 PDE1A, IQCF3, KLK8, CDKN2A, SPANXN5, C16orf90, CD48, TXNDC3 and RAC1 (Fig. 3a). The gene discussed is DEFA3; the disease is metastatic melanoma.