Table 3.

Identified variants in pubertal delay patients.

Gene lists/genes	Variants	Protein variants	Reference	Translational impact	Zygosity	ACMG crtieria	SIFT	PolyPhen-2	Mutation Taster	REVEL	MetaLR
SLDP only
IGSF10	c.7124A>G	p.N2375S		Missense	Het	VUS	X	X	X	X	X
Both SLDP and IHH
GNRHR
	c.317A>G	p.Q106R	(42, 43)	Missense	Hom	P	X	X	X	X	O
	c.436C>T	p.P146S	(44)	Missense	Het	LP	X	X	X	X	X
SEMA3A	c.1849C>T	p.R617Ter		Nonsense	Het	P	–	–	X	–	–
TAC3
	c.209-1G>C	–	(31)	Splice site	Hom	P	–	–	X	–	–
	c.*2-1G>T	–		Splice site	Het	LP	–	–	–	–	–
TACR3	c.1090C>T	p.R364Ter		Nonsense	Het	P	–	–	X	–	–
CHD7	c.3738G>A	p.M1246I		Missense	Het	VUS	X	X	X	X	X
IHH only
DCC	c.1933C>T	p.P645S	(45)	Missense	Het	VUS	X	X	X	O	O
DMXL2	c.2540C>T	p.T847I		Missense	Het	VUS	X	X	X	O	O
KISS1R	c.-249G>A	–		Promoter	Het	VUS	–	–	–	–	–
OTUD4	c.458_460delCTG	p.A153del		In-frame deletion	Het	VUS	–	–	–	–	–
PROKR2	c.809G>A	p.R270H	(46)	Missense	Hom	VUS	X	X	X	X	X
SEMA3E	c.398G>T	p.C133F		Missense	Het	VUS	X	X	X	X	X

X, a potentially deleterious variant by prediction tools (deleterious by SIFT, probably or possibly damaging by PolyPhen2, disease causing by Mutation Taster, likely disease causing by REVEL, and damaging by MetaLR); O, non-pathogenic predicted by prediction tools (tolerated by SIFT, benign or unknown by PolyPhen2, polymorphism by Mutation Taster, likely benign by REVEL, and tolerated by MetaLR); Het, heterozygous; Hom, homozygous; P, pathogenic; LP, likely pathogenic; VUS, variant of uncertain significance.