Extended Data Figure 8.

Stringency of de novo mutation (DNM) filtering. a, Sensitivity and specificity of DNM validations within sets filtered on varying thresholds of DNM quality (posterior probability of DNM). The analysed DNMs were restricted to sites identified within the earlier 1133 trios¹⁵, where all candidate DNMs underwent validation experiments. The labelled value is the quality threshold at which the number of candidate synonymous DNMs equals the number of expected synonymous mutations under a null germline mutation rate. b, Excess of missense and loss-of-function DNMs at varying DNM quality thresholds. The DNM excess is adjusted for the sensitivity and specificity at each threshold.