ArticleEuropean journal of human genetics : EJHG2024
Estimating the proportion of nonsense variants undergoing the newly described phenomenon of manufactured splice rescue.
Article in European journal of human genetics : EJHG, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it.
- International policies guiding the selection, analysis, and clinical management of secondary findings from genomic sequencing: A systematic review.American journal of human genetics · 2024Pooled it
- Article
- UCP3 gene variants and obesity in a Pakistani sample population.Scientific reports · 2025Article
- Assessing Splicing Variants in the PAX6 Gene: A Comprehensive Minigene Approach.Journal of cellular and molecular medicine · 2025Article
- Systematically developing a registry of splice-site creating variants utilizing massive publicly available transcriptome sequence data.Nature communications · 2025Article
- Loss-of-function variants affecting the STAGA complex component SUPT7L cause a developmental disorder with generalized lipodystrophy.Human genetics · 2024Article
- Using exomes better.European journal of human genetics : EJHG · 2024Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
A recent report described a nonsense variant simultaneously creating a donor splice site, resulting in a truncated but functional protein. To explore the generalizability of this unique mechanism, we annotated >115,000 nonsense variants using SpliceAI. Between 0.61% (donor gain delta score >0.8, for high precision) and 2.57% (>0.2, for high sensitivity) of nonsense variants were predicted to create new donor splice sites at or upstream of the stop codon. These variants were less likely than other nonsense variants in the same genes to be classified as pathogenic/likely pathogenic in ClinVar (p < 0.001). Up to 1 in 175 nonsense variants were predicted to result in small in-frame deletions and loss-of-function evasion through this "manufactured splice rescue" mechanism. We urge caution when interpreting nonsense variants where manufactured splice rescue is a strong possibility and correlation with phenotype is challenging, as will often be the case with secondary findings and newborn genomic screening programs.
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Registered trials
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