Fig. 1. Diagram of proposed mechanism by which a nonsense variant could result in aberrant splicing and thus a potentially functional protein product.

A Grossly simplified depiction of the “normal” splicing of a 4-exon protein coding gene. B Example of a sequence variant that could simultaneously result in a stop-gain and in activation of a cryptic 5’ (donor) splice site. If use of the latter results in a small in-frame deletion, there may be a truncated but functional protein product. In the example shown, the pre-mRNA position of the new splice site would be 2 nucleotides upstream of the variant (i.e., delta position = −2). Created with BioRender.com.