Fig. 7.

Brain-specific mutational burden on splicing in ASD. a Tissue-agnostic variant effect prediction with MMSplice. Splice-region de novo mutations (n = 3884, “Materials and methods” section) of the proband group (gray) have significantly lower predicted ΔlogitΨ according to MMSplice compared to those of the unaffected sibling group (orange). The effect size is larger for variants in LoF-intolerant genes (n = 1081). Shown are the means and standard 95% confidence intervals. P values from one-sided Wilcoxon test. b. Tissue-specific variant effect prediction with MTSplice. Distribution of effect size (difference of average ΔlogitΨ for proband versus control siblings de novo mutations) for brain tissues (right boxes) and other tissues (left boxes), and for all de novo mutations (left panel) or de novo mutations in LoF-intolerant genes (right panel) with MTSplice. Individual tissue plots are shown Additional file 1: Fig. S8. The predicted effect sizes are more pronounced for brain tissues