Table 3.

Phenotype and genotype of primary gonadal/genital disorders subjects with P/LP variants.

Patient ID	Age	Phenotype	Transcript ID	Genetic variants	Zygosity	Family inheritance	Inheritance mode	Pathogenicity	gnomAD frequency	Popmax
1880	2 months	Penoscrotal transposition, bifid scrotum	NM_003140.2	SRY c.397C>T, p.Arg133Trp	Hemi	NA	YL	P	/	/
1886	6 months	Ambiguous genitalia, blind perineal pouch resembling vagina, cryptorchidism	NM_000348.3	SRD5A2 c.419_421delinsATTC, p.Trp140Tyrfs*8	Het	F	AR	P	/	/
				SRD5A2 c.680G>A, p.Arg227Gln	Het	M	AR	P	0.0002235	0.004817 (East Asian)
2367	11 years	Predominantly female external genitalia	NM_000102.3	CYP17A1 c.985_987delinsAA, p.Tyr329Kfs*90	Homo	F + M	AR	P	0.00004599	0.0006317 (East Asian)
2420	7 months	Micropenis, cryptorchidism	NM_000348.3	SRD5A2 c.680G>A, p.Arg227Gln	Homo	F + M	AR	P	0.0002235	0.004817 (East Asian)
2439	2 months	Ambiguous external genitalia	NM_004959.4	NR5A1 c.721C>T, p.Arg241Trp	Het	M	AD	LP	/	/
2540	17 years	Predominantly female external genitalia, cryptorchidism	NM_000044.3	AR c.1787G>A, p.Cys596Tyr	Hemi	De novo	XR	P	/	/
2752	1 year	Micropenis, hypogonadism	NM_000044.3	AR c.2528T>C, p.Ile843Thr	Hemi	M	XR	LP	/
2782	2 years 9 months	Perineal hypospadias, micropenis	NM_000348.3	SRD5A2 c.680G>A, p.Arg227Gln	Het	F	AR	P	0.0002235	0.004817 (East Asian)
				SRD5A2 c.281G>A, p.Arg94Lys	Het	M	AR	LP	/	/
2892	7 months	Ambiguous genitalia, micropenis, severe hypospadias, cryptorchidism	NM_000348.3	SRD5A2 c.607G>A, p.Gly203Ser	Het	NA	AR	P	0.00002629	0.0001567 (East Asian)
				SRD5A2 c.737G>A, p.Arg246Gln	Het	NA	AR	LP	0.000126	0.0004087 (South Asian)
3167	6 years	Predominantly female external genitalia, cryptorchidism	NM_000233.3	LHCGR c.681-1Gly>Ala	Het	F	AR	P	/	/
		Predominantly female external genitalia, cryptorchidism		LHCGR c.1582_1585delATAT, p.Ile528*	Het	M	AR	P	/	/
4004	11 years	Micropenis, hypogonadism	NM_000044.3	AR c.1175C>G, p.Pro392Arg	Hemi	M	XR	LP	0.00001776	0
4119	5 years	Micropenis, bilateral cryptorchidism, gonadal dysplasia	NM_003309.3	TSPYL1 c.67C>T, p.Gln23*	Het	De novo	AR	LP	0.0001441	0.001463 (East Asian)
4208	10 months	Female external genitalia, clitoromegaly	NM_000044.3	AR c.2256G>A, p.Trp752*	Hemi	M	XR	P	/	/
4622	1 year 7 months	Hypospadias, penile curvature, cryptorchidism	NM_000348.3	SRD5A2 c.269A>C, p.His90Pro	Het	F	AR	LP	/	/
				SRD5A2 c.680G>A, p.Arg227Gln	Het	M	AR	P	0.0002235	0.004817 (East Asian)
4986	6 months	Ambiguous genitalia, hypospadias, cryptorchidism	NM_004959.4	NR5A1 c.251G>A, p.Arg84His	Het	M	AD	P	/	/
5015	8 months	Cryptorchidism, inguinal fallopian tubes	NM_000479.3	AMH c.585C>A, p.Tyr195*	Het	F	AR	LP	/	/
				AMH c.1165G>T, p.Glu389*	Het	M	AR	LP	0.0000198	/
6791	2 years 9 months	Micropenis	NM_000348.3	SRD5A2 c.680G>A, p.Arg227Gln	Homo	F+M	AR	P	0.0002235	0.004817 (East Asian)
7847	9 years 9 months	Hypospadias, micropenis, penile curvature	NM_000348.3	SRD5A2 c.656delT, p.Phe219Serfs*60	Het	F	AR	P	0.00000657	0
7929	6 years	Penoscrotal hypospadias, cryptorchidism	NM_004959.4	NR5A1 c.848G>T, p.Cys283Phe	Het	M	AD	LP	/	/
8065	10 months	Female external genitalia, cryptorchidism	NM_000044.3	AR del Exon5-8	Hemi	NA	XR	P	/
8803	10 years	Micropenis, hypospadias	NM_000044.4	AR c.2270A>G, p.Asn757Ser	Hemi	M	XR	LP	0.000008892	0
8945	1 month	Hyperpigmentation, cryptorchidism, electrolyte disturbance	NM_000475.4	NR0B1 c.1169-2Ala>Gly	Hemi	De novo	XL	P	/	/
9052	1 year	Female external genitalia, cryptorchidism	NM_000044.4	AR c.2495G>A, p.Arg832Gln	Hemi	M	XR	LP	0.000008987	0
9242	1 year 3 months	Perineal hypospadias, bifid scrotum	NM_000348.3	SRD5A2 c.650C>A, p.Ala217Glu	Het	F	AR	LP	/	/
				SRD5A2 c.680G>A, p.Arg227Gln	Het	M	AR	P	0.0002235	0.004817 (East Asian)
9431	3 years 1 month	Ambiguous genitalia, cryptorchidism	NM_000348.3	SRD5A2 c.607G>A, p.Gly203Ser	Het	F	AR	P	0.00002629	0.0001567 (East Asian)
				SRD5A2 c.680G>A, p.Arg227Gln	Het	M	AR	P	0.0002235	0.004817 (East Asian)
9471	12 years	Predominantly female external genitalia, clitoromegaly, cryptorchidism	NM_000044.4	AR c.4G>A, p.Glu2Lys	Hemi	M	XR	LP	/
9482	5 years	Micropenis, cryptorchidism	NM_000348.3	SRD5A2 c.680G>A, p.Arg227Gln	Homo	F + M	AR	P	0.0002235	0.004817 (East Asian)
10066	5 months	Micropenis, cryptorchidism	NM_000044.4	AR c.899G>C, p.Gly300Ala	Hemi	M	XR	LP	0.00002657	0.00001494 (European)
10239	2 years	Bilateral cryptorchidism, motor development retardation, ptosis, short stature, hydrocephalus	/	7q33-q35Del	Het	M	-	P	/	/
10482	7 years 6 months	Bilateral cryptorchidism, short stature, funnel chest	NM_002934.4	PTPN11 c.1472C>A, p.Pro491His	Het	De novo	AD	P	/	/
10800	2 months 12 days	Hypospadias, penoscrotal transposition, micropenis, bifid scrotum	/	2q33.1Del	Het	De novo	-	LP	/	/
10892	3 years 5 months	Unilateral cryptorchidism, short stature	NM_002934.4	PTPN11 c.922A>G, p.Asn308Asp	Het	De novo	AD	P	0.00001193	0
10908	14 years 6 months	Female external genitalia, cryptorchidism, gynecomastia	NM_000044.4	AR c.1737delC, p.Cys580Alafs*46	Hemi	M	XR	P	/	/
11072	15 years 6 months	Female external genitalia, cryptorchidism, clitoromegaly	NM_000044.4	AR c.2113C>T, p.Leu705Phe	Hemi	M	XR	LP	/
11757	8 months	Hypospadias, micropenis	NM_000348.3	SRD5A2 c.16C>T, p.Gln6*	Het	M	AR	P	/	/
				SRD5A2 c.680G>A, p.Arg227Gln	Het	F	AR	P	0.0002235	0.004817 (East Asian)
11867	6 months	Micropenis	NM_000348.3	SRD5A2 c.680G>A, p.Arg227Gln	Homo	F + M	AR	P	0.0002235	0.004817 (East Asian)
12480	5 years	Bilateral cryptorchidism, mental retardation, intelligence disability, ptosis, strabismus	/	18p11.31-p11.21del	Het	De novo	-	P	/	/
12888	13 years	Bilateral cryptorchidism, micropenis, intelligence disability	/	16p11.2del	Het	De novo	-	P	/	/
13048	5 years	Micropenis, mental retardation	/	17p11.2del	Het	De novo	-	P	/	/
13421	4 years	Micropenis, hypospadias, penoscrotal transposition	NM_000044.4	AR c.2020T>C, p.Phe674Leu	Hemi	M	XR	LP	/	/
14250	4 months 3 days	Micropenis, hypospadias, bifid scrotum	NM_000348.3	SRD5A2 c.607G>A, p.Gly203Ser	Het	F	AR	P	0.00002629	0.0001567 (East Asian)
				SRD5A2 c.680G>A, p.Arg227Gln	Het	M	AR	P	0.0002235	0.004817 (East Asian)
15362	1 year 9 months	PMDS, transverse testicular ectopia	NM_000479.3	AMH c.259-270del, p.Val187-Ala90del	Het	M	AR	LP	/	/
				AMH c.1432C>T, p.Leu478Phe	Het	F	AR	LP	/	/
16213	3 years 11 months	Micropenis	NM_000348.3	SRD5A2 c.680G>A, p.Arg227Gln	Homo	F + M	AR	P	0.0002235	0.004817 (East Asian)
16746	5 years 4 months	Micropenis	NM_000348.3	SRD5A2 c.680G>A, p.Arg227Gln	Homo	F + M	AR	P	0.0002235	0.004817 (East Asian)
18423	6 years 10 months	Bilateral cryptorchidism, dysmorphic facial features (ocular hypertelorism, low nose bridge, flapping ear, ptosis), chicken breast, lumbar lateral curvature, brachydactylia, pulmonic stenosis, atrial septal defect, patent foramen ovale, lymphangioma of right lower limb	NM_006912.6	RIT1 c.170C>G, p.Ala57Gly	Het	F	AD	P	/	/
18553	11 years 9 months	Micropenis	NM_000348.3	SRD5A2 c.680G>A, p.Arg227Gln	Homo	F + M	AR	P	0.0002235	0.004817 (East Asian)
19697	2 years 8 months	Micropenis	NM_000348.3	SRD5A2 c.467G>A, p.Gly156Glu	Het	M	AR	LP	0.000006677	0
20472	13 years 10 months	Hypospadias, penoscrotal transposition	NM_000044.6	AR c.2521C>T, p.Arg841Cys	Hemi	M	XR	LP	/	/
				AR c.1175C>G, p.Pro392Arg	Hemi	M	XR	LP	0.00001776	0

AD, autosomal dominant; AR, autosomal recessive; F, father; Hemi, hemizygote; Het, heterozygote; Homo, homozygote; LP, likely pathogenic; M, mother; P, pathogenic; PMDS, persistent Müllerian duct syndrome; XL, X chromosome linked; YL, Y chromosome linked.