Table 3.

Variants in candidate genes

	Loss-of-function variants in 543 published ID candidate genes
ID	Gene	Inheritance	Mutation	Effect	Gene/protein function	Patient phenotype
S_085	BPTF (NM_182641.3)	de novo	c.989del	p.(Leu330Argfs*28)	Bromodomain PHD finger transcription factor; expressed in fetal brain; potential transcriptional regulator; 4 de novo variants in DDD (McRae)	IQ 54, mild short stature, microcephaly, sleeping difficulties, sometimes aggressivity
S_104	ZNF292 (NM_015021.1)	de novo	c.3066_3069del	p.(Glu1022Aspfs*3)	Homo sapiens zinc finger protein 292; possible growth hormone dependent transcription factor; 1 SNV and 1 LOF variant in DDD (McRae)	Developmental delay, constipation, feeding difficulties, hypothyreosis, short stature, facial dysmorphism

	Loss-of-function variants in 1694 constrained (haploinsufficiency intolerant) genes
S_115	LRRC7 (NM_020794.2)	de novo	c.3516T>G	p.(Tyr1172*)	leucine-rich repeat-containing protein 7; scaffold protein of post-synaptic densities	IQ 70, absence epilepsy during first years, obesity, muscle and joint pain, migraine
S_013	JAKMIP1 (NM_001099433.1)	no parental samples	c.1432-2A>G	r.(spl?)	janus kinase and microtubule interacting protein 1; highly expressed in brain; interaction with GABBR1	Feeding difficulties, hypotonia, epilepsy, severe ID, no active speech, kyphoscoliosis, constipation, autism, short stature
S_012	PUM1 (NM_001020658.1)	not maternal	c.1158+1_1158+2dup	r.(spl?)	pumilio homolog 1; potential translational regulator of embryogenesis, cell development and differentiation; 1 de novo LOF variant in DDD (McRae)	Developmental delay, normal motor milestones, speech delay, anomalies of palmar creases
S_012	ZMYND8 (NM_001281775.2)	not maternal	c.2629C>T	p.(Gln877*)	Homo sapiens zinc finger, MYND-type containing 8; potential involvement in cell signaling, actin dynamics, transcriptional regulation

Additional genomic references for the intronic splice variants: NC_000004.11(JAKMIP1):g.6064169T>C; NC_000001.10(PUM1):g.31465235_31465236dup