A new plugin was released in Ensembl VEP version 105 which reports when a variant introducing a premature stop codon may allow the transcript to escape nonsense-mediated decay (NMD).
A variant introducing a premature stop codon in a transcript may result in a truncated protein. This could cause problems as it won’t have the functionality of the normal protein and could have unusual and deleterious effects. Nonsense-mediated mRNA decay is a molecular mechanism for removing such truncated proteins, but variants falling in certain locations in a transcript may allow this mechanism to be escaped.
The NMD plugin analyses the location of ‘stop gained’ variants with respect to the overlapping transcript to predict whether the transcript encoding the truncated protein is likely to escape NMD-mediated degradation. The Sequence Ontology term ‘NMD_escaping_variant’ is applied when a ‘stop gained’ variant falls in any of these locations:
- the last coding exon of a transcript
- the last 50 bases of the penultimate coding exon of a transcript
- the first 100 bases of the coding sequence in the transcript
- an intronless transcript
We have matched the criteria used to define NMD-escape with the DECIPHER project. This plugin is currently available for command line use.