Somatic single nucleotide variants (SNVs) are genomic events with increasing implications in cancer treatment. The clinical standard for SNVs detection is whole genome/exome sequencing (WGS/WES) in matched tumor-normal samples. Yet, this is a very costly approach both economically and biologically and very often only tumor samples are sequenced. On the other hand, RNA sequencing (RNA-Seq) is the most popular technology to study gene expression, and has also the potential for a cost-effective identification of SNVs as an alternative to tumor-only WES. Here we present a method for the identification of SNVs in tumor-only RNA-Seq data putting a special focus on a small panel of clinically relevant SNVs. For evaluation purposeswe analyzed matched tumor-normal WEStumor-only RNA-Seq data from 14 cancer patients. We compared SNVs detected in i) RNA-Seq by our method, ii) WES tumor-only by Mutect2 and iii) WES matched tumor-normal by Mutect2. We did a detailed evaluation for a reduced panel of clinically relevant SNVs and reliably identified in RNA-Seq data a subset of mutations for which we had pathological annotation. Hence, RNA-Seq rises as a cost-effective option to detect in parallel gene expression as well as a small panel of clinically relevant SNVs in research.