NMD Escape Tracks

NMD Escape: Predicted regions where premature termination codons escape NMD tracks (All Genes and Gene Predictions tracks)

Show or hide this container and all tracks: Reset to defaults

Tracks that are part of this container are listed below. Use the buttons below to set their visibility. The grey button shows each track's current visibility.

Apply visibility:
	NMD Escape MANE	NMD escape predictions: MANE Select Plus Clinical transcripts Version: MANE 1.5
	NMD Escape Gencode	NMD escape predictions: Gencode transcripts Version: Gencode V49
	NMD Escape RefSeq	NMD escape predictions: NCBI RefSeq Curated transcripts Version: GCF_000001405.40-RS_2025_08
	NMDetective-AI	NMDetective-AI: Deep-learning NMD efficiency prediction per position (MANE Select only)
	NMDetective-AI variants	NMDetective-AI: Per-stop-gain predictions for every codon (MANE Select only)
	NMDetective-A	NMDetective-A: Random forest prediction of NMD efficiency (Lindeboom 2016)
	NMDetective-B	NMDetective-B: Decision tree prediction of NMD efficiency (Lindeboom 2016)
	NMDetective-A PTC	NMDetective-A: Random forest NMD efficiency for first out-of-frame PTC
	NMDetective-B PTC	NMDetective-B: Decision tree NMD efficiency for first out-of-frame PTC

Related tracks

MANE: MANE Select transcripts from NCBI/EBI, a curated subset of RefSeq/Ensembl transcripts used as clinical reference
RefSeq All: NCBI RefSeq transcripts, the source annotation set for the NMD Escape RefSeq subtrack

Assembly: Human Dec. 2013 (GRCh38/hg38)

new Note: Released Apr. 22, 2026

Description

NMD is a cellular quality control mechanism that detects and degrades mRNAs containing premature termination codons (PTCs), preventing the accumulation of truncated, potentially harmful proteins. However, not all PTCs trigger NMD. PTCs in certain regions of a transcript are predicted to escape NMD, meaning the truncated mRNA may be translated into a protein with unpredictable functional consequences. The NMD Escape container includes several tracks that display putative regions where PTC variants are assumed to escape the NMD mechanism. These are typically located close to the first or last splice junction, within unusually long coding exons, or in transcripts without any junction.

Subtracks

NMD escape regions

Rule-based predictions of NMD escape regions, computed from transcript annotations. Three transcript sets are provided:

NMD escape MANE: NMD escape regions derived from the MANE Select plus MANE Plus Clinical transcript set, a jointly curated NCBI/EBI annotation that defines a single high-confidence transcript per protein-coding gene (Select), supplemented by additional transcripts of clinical importance (Plus Clinical).
NMD escape Gencode: NMD escape regions derived from GENCODE V49 transcripts.
NMD escape NCBI RefSeq: NMD escape regions derived from NCBI RefSeq Curated transcripts (NM_ and NR_ accessions only).

Click either of the links to the track details here or above to show the four rules that were used (50 bp, intronless, 100 bp, long exon >400 nt).

NMDetective scores

Machine-learning predictions of NMD efficiency from Lindeboom et al. 2016 (A and B models) and from Veiner et al. (NMDetective-AI, pre-print 2026). Positive scores indicate predicted NMD triggering; negative scores indicate predicted escape.

NMDetective-A: Random forest model for all possible PTCs from nonsense variants.
NMDetective-B: Decision tree model for all possible PTCs from nonsense variants.
NMDetective-A PTC: Random forest model for the first out-of-frame PTC from frameshifting indels.
NMDetective-B PTC: Decision tree model for the first out-of-frame PTC from frameshifting indels.
NMDetective-AI and NMDetective-AI variants: Deep-learning model on MANE Select transcripts (GENCODE V46). Signal track shows the position-averaged prediction; variants track shows one item per stop-gain mutation per codon.

Background

The ACMG guidelines say under PVS1:

(ii) One must also be cautious when interpreting truncating variants downstream of the most 3′ truncating variant established as pathogenic in the literature. This is especially true if the predicted stop codon occurs in the last exon or in the last 50 base pairs of the penultimate exon, such that nonsense-mediated decay would not be predicted, and there is a higher likelihood of an expressed protein.

Data Access

The data underlying these tracks can be explored interactively with the Table Browser or the Data Integrator. For automated analysis, the data may be queried from our REST API. Please refer to our mailing list archives for questions, or our Data Access FAQ for more information.

Credits

Thanks to Guido Neidhardt for suggesting this track at HUGO VEPTC 2025 and Andreas Lahner for feedback. Thanks to the Decipher Genome Browser team for introducing the idea of a track. Thanks to Rik Lindeboom for providing custom tracks.

References

Kurosaki T, Popp MW, Maquat LE. Quality and quantity control of gene expression by nonsense-mediated mRNA decay. Nat Rev Mol Cell Biol. 2019 Jul;20(7):406-420. PMID: 30992545; PMC: PMC6855384

Lindeboom RGH, Supek F, Lehner B. The rules and impact of nonsense-mediated mRNA decay in human cancers. Nat Genet. 2016 Oct;48(10):1112-8. PMID: 27618451; PMC: PMC5045715

Lindeboom RGH, Vermeulen M, Lehner B, Supek F. The impact of nonsense-mediated mRNA decay on genetic disease, gene editing and cancer immunotherapy. Nat Genet. 2019 Nov;51(11):1645-1651. PMID: 31659324; PMC: PMC6858879

Nagy E, Maquat LE. A rule for termination-codon position within intron-containing genes: when nonsense affects RNA abundance. Trends Biochem Sci. 1998 Jun;23(6):198-9. PMID: 9644970