We also identified an individual with excess minor intron retention events who had rare, highly conserved, compound heterozygous variants in RNU6ATAC that may disrupt the formation of the catalytic spliceosome, suggesting a novel gene-disease candidate!

By examining the RNA-seq data of 390 individuals in a rare disease cohort for patterns of minor intron retention events, we were able to identify four individuals with RNU4atac-opathies, a difficult-to-diagnose disease, caused by biallelic variants in RNU4ATAC (as well as reclassify four variants!).