Table 1.

Novel variants predictive of ovarian failure. Chromosomal and genomic positions of the variants, as well as bases and amino acid changes at the indicated number in the sequences, dbSNP IDs (if known), type of changes, amino acid class, polarity and charge changes, genes affected, number of cases affected by the variant, coverage (mean and standard deviation), and accession numbers. Variants were present in at least 10% of cases (12 women out of 118) and no controls. Gene Ontology and Genecards databases were consulted to annotate gene function. ¹ Top 6 variants shared by >20 cases. ² Top variants valued by random forest algorithm to stratify the population. ³ The three variants found affecting genes already related to ovarian failure in the literature. ⁴ Variant absent in International Genome Sample Resource, dbSNP, and GnomAD databases.

Chromosome and Position	Change at Sequence and Aa Level	Rs	Type of Change	Amino Acid Class, Polarity, and Charge Change	Gene	Function	N Cases Affected	Coverage	Accession Number
2; 84897501 2	c.6356A > G, p.Tyr2119Cys	rs17025409	Missense variant	Aromatic polar neutral > sulfuric nonpolar neutral	DNAH6	Microtubule activity	17	146 (18.08)	NM_001370.1
2; 84932720 2	c.8576A > G, p.Lys2859Arg	rs61750773	Missense variant	Basic polar positive > basic polar positive	DNAH6	Microtubule activity	19	146 (20.02)	NM_001370.1
2; 85059227 2	c.1034C > T, p.Arg345His	rs61744273	Missense variant	Basic polar positive > basic aromatic polar positive-neutral	TRABD2A	Negative regulation of WNT signalling pathway	18	287 (42.23)	NM_001277053.1
5; 79950724 3	c.181G > C, p.Ala60Pro	rs2001675	Missense variant	Aliphatic nonpolar neutral > cyclic nonpolar neutral	MSH3	DNA repair	15	145 (57.73)	NM_002439.4
6; 36168628 1	c.529A > G, p.Ser177Gly	rs45504893	Missense variant	Hydroxylic polar neutral > aliphatic nonpolar neutral	BRPF3	Chromatin organisation	22	320 (44.1)	NM_015695.2
9; 69391207 4	c.715G > A, p.Ala239Thr		Missense variant	Aliphatic nonpolar neutral > hydroxylic polar neutral	ANKRD20A4	Unknown	13	125 (8.03)	NM_001098805.1
11; 1017471 2	c.5330G > A, p.Gly1777Asp		Missense variant	Aliphatic nonpolar neutral > acid acidic polar negative	MUC6	Cytoprotection of epithelial surfaces	13	448 (194.38)	NM_005961.2
11; 1017504 1,2	c.5297C > T, p.Thr1766Ile		Missense variant	Hydroxylic polar neutral > aliphatic nonpolar neutral	MUC6	Cytoprotection of epithelial surfaces	31	448 (147.15)	NM_005961.2
14; 57755564 1	c.1435G > A, p.Ala479Thr	rs35759976	Missense variant	Aliphatic nonpolar neutral > hydroxylic polar neutral	AP5M1	Apoptosis	22	179 (14.19)	NM_018229.3
16; 25239809 2,3	c.782G > A, p.Arg261Gln	rs111840156	Missense variant	Basic polar positive > amide polar neutral	AQP8	Cellular response to cAMP	13	265 (24.69)	NM_001169.2
16; 84902483 1	c.880A > T, p.Met294Leu	rs72799568	Missense variant	Sulfuric nonpolar neutral > aliphatic nonpolar neutral	CRISPLD2	Extracellular matrix assembly	21	247 (145.71)	NM_031476.3
16; 88902199 1	c.692C > G, p.Ala237Gly	rs34745339	Structural interaction variant, missense variant	Aliphatic nonpolar neutral > aliphatic nonpolar neutral	GALNS	Degradation of glycosaminoglycans	20	214 (33.02)	NM_000512.4
17; 71232990 2	c.1369C > A, p.Arg457Ser	rs61729639	Missense variant	Basic polar positive > hydroxylic polar neutral	SPEP1	Unknown	14	180 (38.16)	NM_001288771.1
22; 17450929 2	c.841G > A, p.Ala281Thr	rs61741409	Missense variant	Aliphatic nonpolar neutral > hydroxylic polar neutral	GAB4	Unknown	14	236 (36.89)	NM_001037814.1
22; 17450952 2	c.818T > C, p.Leu273Pro	rs11703655	Missense variant	Aliphatic nonpolar neutral > cyclic nonpolar neutral	GAB4	Unknown	14	236 (43.66)	NM_001037814.1
22; 25024326 3	c.1534G > A, p.Val512Ile		Structural interaction variant, missense variant	Aliphatic nonpolar neutral > aliphatic nonpolar neutral	GGT1	Proteolysis	14	112 (17.48	NM_013430.2
22; 35802661 1	c.539C > G, p.Thr180Ser	rs2307340	Missense variant	Hydroxylic polar neutral > hydroxylic polar neutral	MCM5	DNA replication initiation	20	309 (92.27)	NM_006739.3