Fig. 1

Functional annotation of 5’UTR variants, filtering, and prioritization strategy followed in this study. A combination of in silico tools (see “Methods”) was used to annotate 5’UTR variants, which were then classified into 7 functional categories. For each of these categories, specific criteria were established for prioritizing variants with a more likely functional impact (bottom). Only variants with a minor allele frequency (MAF) <2% were further studied. The following information was then reviewed: inheritance pattern of the family (AR including sporadic cases; AD; XL) and clinical features. For the selection of candidate variants, both had to be in agreement with the reported mode of inheritance and phenotype associated with the gene in which the 5’UTR variant was found. AD autosomal dominant, AR autosomal recessive, FC fold change, IRES internal ribosomal entry site, TE translational efficiency, TSS transcription start site, uAUG upstream AUG, uORF upstream open reading frame