ArticleNature communications2017
Annotating pathogenic non-coding variants in genic regions.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 154 citations in OpenAlex.
- Predicting Functional Effects of Synonymous Variants: A Systematic Review and Perspectives.Frontiers in genetics · 2019Pooled it
- Analysis of transcript-deleterious variants in Mendelian disorders: implications for RNA-based diagnostics.Genome biology · 2020Trial
- SIMLINK enables accurate variant pathogenicity prediction through modeling the gene-variant-feature association structure.Bioinformatics (Oxford, England) · 2026Article
- Genetic studies identify known and novel variants for recessively inherited moderate to severe hearing loss in consanguineous families from Pakistan.Scientific reports · 2026Article
- CDsyn: A comprehensive database for deleterious human synonymous variation prediction.iScience · 2026Article
- Interstitial cystitis: a phenotype and rare variant exome sequencing study.EBioMedicine · 2026Article
- Synonymous Variants of Potential Significance Identified by a 52-Gene Clinical Sequencing Panel in Non-Small Cell Lung Cancer.Genes, chromosomes & cancer · 2026Article
- Evolving computational paradigms for noncoding variant pathogenicity prediction.Frontiers in molecular biosciences · 2026Review
- Rare missense variants inFrontiers in genetics · 2026Article
- Genome-wide functional annotation and interpretation of splicing variants: toward RNA-targeted therapies.Journal of human genetics · 2025Review
- Functional synonymous mutations and their evolutionary consequences.Nature reviews. Genetics · 2025Review
- DRP-PSM: Multi-Level Feature Integration Reveals Hierarchical Contributions to Pathogenic Synonymous Mutation Prediction.ACS omega · 2025Article
- Prediction of human pathogenic start loss variants based on self-supervised contrastive learning.BMC biology · 2025Article
- Exome analysis links kidney malformations to developmental disorders and reveals causal genes.Nature communications · 2025Article
- Comprehensive functional splicing analysis of non-canonical CNGB3 variants using in vitro minigene splice assays.The Journal of pathology · 2025Article
- Ensemble learning-based predictor for driver synonymous mutation with sequence representation.PLoS computational biology · 2025Article
- A second hotspot for pathogenic exon-skipping variants in CDC45.European journal of human genetics : EJHG · 2024Article
- Article
- Variant ranking pipeline for complex familial disorders.Scientific reports · 2024Article
- Detecting and understanding meaningful cancerous mutations based on computational models of mRNA splicing.NPJ systems biology and applications · 2024Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Identifying the underlying causes of disease requires accurate interpretation of genetic variants. Current methods ineffectively capture pathogenic non-coding variants in genic regions, resulting in overlooking synonymous and intronic variants when searching for disease risk. Here we present the Transcript-inferred Pathogenicity (TraP) score, which uses sequence context alterations to reliably identify non-coding variation that causes disease. High TraP scores single out extremely rare variants with lower minor allele frequencies than missense variants. TraP accurately distinguishes known pathogenic and benign variants in synonymous (AUC = 0.88) and intronic (AUC = 0.83) public datasets, dismissing benign variants with exceptionally high specificity. TraP analysis of 843 exomes from epilepsy family trios identifies synonymous variants in known epilepsy genes, thus pinpointing risk factors of disease from non-coding sequence data. TraP outperforms leading methods in identifying non-coding variants that are pathogenic and is therefore a valuable tool for use in gene discovery and the interpretation of personal genomes.While non-coding synonymous and intronic variants are often not under strong selective constraint, they can be pathogenic through affecting splicing or transcription. Here, the authors develop a score that uses sequence context alterations to predict pathogenicity of synonymous and non-coding genetic variants, and provide a web server of pre-computed scores.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.