Variant Attributes (6 points max): These include conservation (GERP++), "in silico" predictions (MutationAssessor, MutationTaster, Sift), splice site predictions (MaxEntScan, AdaBoost, RandomForest) and expected impact (VEP).
Gene Constraints (1 point max): These are gene constraint parameters from gnomAD; LOUEF for loss of function variants, Z for missense variants.
Inheritance (2 points max): These points depend on inheritance of the variant of interest and segregation of the variant in the family.
Gene Plausibility (6 points max): These points are calculated based on the gene's expression pattern, protein-protein interactions, animal model phenotypes, published articles on PubMed, de novo variants in the gene linked to NDD and other sources.