By whole-genome sequencing of a trio of affected offspring, sire and dam, Jacinto et al. (2022) "identified two heterozygous private protein-changing variants present exclusively in the genome of the affected calf and absent in both parental genomes as well as in 5365 controls . . . . Only one of these variants was in a putative candidate gene for the observed phenotype. This heterozygous variant at chr10:84751870G>A (NM_001101951.1: c.416C>T) represents a missense variant in a splicing region located in exon 7 of the NUMB endocytic adaptor protein (NUMB) gene . . . . The guanine to arginine substitution affects an evolutionary highly conserved amino acid (NP_001095421.1: p.Thr139Met) in the phosphotyrosine interaction domain (PTB/PID) and was predicted to be deleterious using four different tools (provean, −2.599; polyphen, 2: 56%; sift, 79%; and mapp, 57%). Sanger sequencing confirmed the presence of the heterozygous NUMB variant in the affected calf and its sire, which clearly carried the mutant allele at a low level in comparison with the wild type allele, representing a germinal mosaic".
