ArticleAmerican journal of human genetics2023
Using the ACMG/AMP framework to capture evidence related to predicted and observed impact on splicing: Recommendations from the ClinGen SVI Splicing Subgroup.
Article in American journal of human genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 253 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
253 citing papers in PubMed, 1 synthesis or guideline pooled it, 266 citations in OpenAlex.
- The Clinical Pharmacogenetics Implementation Consortium's consensus-based framework for assigning allele function.American journal of human genetics · 2025Guideline
- Rapid minigene workflow for functional reclassification of splicing variants in hereditary cancer diagnostics.Journal of medical genetics · 2026Article
- Splice-site variants in neurology: from molecular mechanisms to clinical interpretation - a focused review.Neurogenetics · 2026Review
- Mutational Spectrum of DMD Gene Variants and Cascade Screening Outcomes in the Central-Eastern Black Sea Region of Türkiye: A Single-Centre Retrospective Study.Molecular biology reports · 2026Article
- Novel Compound-Heterozygous Variants in PYCR1 Expand the Variant Spectrum of Autosomal Recessive Cutis Laxa.Genes · 2026Article
- Pathogenicity assessment of genetic variants in reproductive disorders.Journal of assisted reproduction and genetics · 2026Review
- Review
- Long-read sequencing reveals a hidden Alu-mediated splice defect in CPLANE1, causing orofaciodigital syndrome type VI.European journal of human genetics : EJHG · 2026Article
- Minigene-based characterization and classification of splice-associated variants in succinate dehydrogenase B.NPJ precision oncology · 2026Article
- Article
- Development of RS1-specific ACMG/AMP variant classification criteria with pilot variant curation.Human genetics · 2026Article
- Beyond in silico prediction: multi-omics to identify a pathogenic deep intronic HNRNPK variant in Au-Kline syndrome.Journal of human genetics · 2026Article
- Long-read transcriptome analysis using IsoRanker for identifying pathogenic variants in Mendelian conditions.American journal of human genetics · 2026Article
- Sequencing approaches in hereditary cancer testing: strengths, limitations and future directions.European journal of human genetics : EJHG · 2026Review
- FIGLA Novel Variant c.385-9G>A Affects RNA Splicing in a Minigene Assay.Annals of human genetics · 2026Article
- The prevalence of protein misfolding as a mechanism for hereditary deafness.PLoS genetics · 2026Article
- Germline whole-exome sequencing identifies CTNND1 as a candidate gene for hereditary gastric cancer in a large Brazilian cohort.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2026Article
- Extending the global landscape of Bruck syndrome: Case series of Indonesian and Ukrainian patients with PLOD2 pathogenic variants and literature review.Bone reports · 2026Article
- RNA sequencing resolves a novel noncanonical splice-region variant inTranslational pediatrics · 2026Article
- Review
193 more citing papers are in PubMed but not listed here.
Corrections and comments
- Update of
Authors and funding
17 authors at 7 institutions in 4 countries.
Funding
Abstract
The American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP) framework for classifying variants uses six evidence categories related to the splicing potential of variants: PVS1, PS3, PP3, BS3, BP4, and BP7. However, the lack of guidance on how to apply such codes has contributed to variation in the specifications developed by different Clinical Genome Resource (ClinGen) Variant Curation Expert Panels. The ClinGen Sequence Variant Interpretation Splicing Subgroup was established to refine recommendations for applying ACMG/AMP codes relating to splicing data and computational predictions. We utilized empirically derived splicing evidence to (1) determine the evidence weighting of splicing-related data and appropriate criteria code selection for general use, (2) outline a process for integrating splicing-related considerations when developing a gene-specific PVS1 decision tree, and (3) exemplify methodology to calibrate splice prediction tools. We propose repurposing the PVS1_Strength code to capture splicing assay data that provide experimental evidence for variants resulting in RNA transcript(s) with loss of function. Conversely, BP7 may be used to capture RNA results demonstrating no splicing impact for intronic and synonymous variants. We propose that the PS3/BS3 codes are applied only for well-established assays that measure functional impact not directly captured by RNA-splicing assays. We recommend the application of PS1 based on similarity of predicted RNA-splicing effects for a variant under assessment in comparison with a known pathogenic variant. The recommendations and approaches for consideration and evaluation of RNA-assay evidence described aim to help standardize variant pathogenicity classification processes when interpreting splicing-based evidence.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.