SHANK3 and Cognitive impairment: We calculated the burden of cognitive impairment (see Methods) in 87 ASD individuals with high-confidence LoF variants in the four novel moderate-risk genes and compared it with that in 129 individuals with high-confidence LoF in the well-established ASD risk genes CHD8, SCN2A, SHANK3, ADNP and FOXP1, as well as 8,731 individuals with ASD (Supplementary Fig. 11).