For example, SHANK3 was disrupted in one individual by pdSNV (nonsense variant) and three individuals by pdCNV (22q13.3 deletion); SHANK3 encodes a scaffold protein of the postsynaptic density that is essential for proper functioning of the synapse and loss of one functional copy of this gene, leading to Phelan-McDermid syndrome, has been estimated to account for ~0.5% of ASD [43]. This evidence concerns the gene SHANK3 and Phelan-McDermid syndrome.