Fig. 1

Overview of the splicing region. a The spliceosome attaches to pre-mRNA as it is transcribed from DNA, removing introns and leaving an exon junction complex upstream. The mature mRNA can migrate out of the nucleus for translation. b Motifs of the polypyrimidine tract, acceptor, and donor, calculated from all protein-coding exons. c Odds ratios of observed and expected variant frequencies around the splice site based on ExAC exome sequencing data in Zhang et al. [4]. Lord et al. [3] use the same ExAC data to calculate the mutability-adjusted proportion of singletons (MAPS) across splicing regions, which is higher at nucleotides intolerant of variation. Jaganathan et al. [5] developed SpliceAI, a neural network for predicting the impact of variants on splicing across the genome; the number of potential variants with a Δ score ≥ 0.1 is shown across splicing regions. Abbreviations: TSS, transcription start site; UTR, untranslated region; A, acceptor; D, donor; Pol II, polymerase II; Ter, termination codon; Poly(A), polyadenylation