Table 1. Female infertility-associated genetic variants affecting prophase I and meiotic entry.
Genes are listed in order of appearance in text; their variants are listed in order of publication year. Frequencies of small (<1kb) genetic variants were identified in gnomAD v2.1.1 and ExAc v1.0 via ANNOVAR. Allele frequencies of structural variants reflect those of overlapping variants of the same type (i.e., deletion (DEL), duplication (DUP) etc.), rather than of exact matches; the gnomAD variant ID of the variant used is indicated.
| Gene | DNA Variant | Protein Variant | Key Phenotype | Reference | Allele Frequency | ||||
|---|---|---|---|---|---|---|---|---|---|
| gnomAD exomes1 | ExAc2 | gnomAD SVs3 | gnomAD genomes4 | ||||||
| DEL | DUP | ||||||||
| SYCP3 | NM_153694.1:c.553–16_19del | Intronic variant | Recurrent pregnancy loss | Bolor et al. (2009)† | NR | ||||
| SYCP3 | NM_153694.1:c.657T>C | Splice donor site variant | Recurrent pregnancy loss | Bolor et al. (2009)† | 5.63E-05 | 6.83E-05 | |||
| SYCP3 | NM_153694.1:c.657T>C | Splice donor site variant | Recurrent pregnancy loss | Mizutani et al. (2011)† | 5.63E-05 | 6.83E-05 | |||
| SYCP3 | NM_153694.1:c.657T>C | Splice donor site variant | Recurrent pregnancy loss | Sazegari et al. (2014)† | 5.63E-05 | 6.83E-05 | |||
| SYCE1 | NC_000010.10:g.135092227_135256027del | Structural variant | Primary ovarian insufficiency | McGuire et al. (2011)† | 1.52E-03 (10_115557) | ||||
| SYCE1 | NM_130784.2:c.613C>T | p.Q205* | Primary ovarian insufficiency | DeVries et al. (2014) | NR | ||||
| SYCE1 | NC_000010.10:g.135254039_135377532dup | Structural variant | Primary ovarian insufficiency | Jaillard et al. (2016)† | 4.97E-02 (10_31262) | ||||
| SYCE1 | NC_000010.10:g.135256762_135379710dup | Structural variant | Primary ovarian insufficiency | Tsuiko et al. (2016)† | 4.97E-02 (10_31262) | ||||
| SYCE1 | NC_000010.10:g.135281682_135377532dup | Structural variant | Primary ovarian insufficiency | Bestetti et al. (2019)† | 4.97E-02 (10_31262) | ||||
| SYCE1 | NC_000010.10:g.135281682_135378761dup | Structural variant | Primary ovarian insufficiency | Bestetti et al. (2019)† | 4.97E-02 (10_31262) | ||||
| SYCE1 | NC_000010.10:g.135252327_135378761dup | Structural variant | Primary ovarian insufficiency | Bestetti et al. (201)† | 4.97E-02 (10_31262) | ||||
| SYCE1 | NC_000010.10:g.135252327_135378761del | Structural variant | Primary ovarian insufficiency | Bestetti et al. (2019)† | 1.52E-03 (10_115557) | ||||
| SYCE1 | NC_000010.10:g.135281682_135404523dup | Structural variant | Primary ovarian insufficiency | Bestetti et al. (2019)† | 4.97E-02 (10_31262) | ||||
| TRIP13 | NM_004237.4: c.77A>G | p.H26R | Oocyte maturation arrest | Zhang et al. (2020b) | 9.19E-06 | 3.21E-05 | |||
| TRIP13 | NM_004237.4:c.518G>A | p.R173Q | Oocyte maturation arrest | Zhang et al. (2020b) | 7.95E-06 | 1.65E-05 | |||
| NM_004237.4:c.907G>A | p.E303K | Oocyte maturation arrest | Zhang et al. (2020b) | 1.60E-05 | 1.65E-05 | ||||
| TRIP13 | NM_004237.4:c.592A>G | p.I198V | Oocyte maturation arrest | Zhang et al. (2020b) | NR | ||||
| NM_004237.4:c.739G>A | pV247M | NR | |||||||
| STAG3 | NM_001282716:c.877_885del | p.293_295del | Primary ovarian insufficiency | Xiao et al. (2019)† | NR | ||||
| STAG3 | NM_001282716:c.891_893dup | p.297_298insAsp | Primary ovarian insufficiency | Xiao et al. (2019)† | NR | ||||
| STAG3 | NM_001282716:c.291dup; | p.N98Qfs*2 | Primary ovarian insufficiency | Franca et al. (2019)† | NR | ||||
| NM_001282716:c.1950C>A | p.Y650* | NR | |||||||
| STAG3 | NM_01282717:c.677C>G | p.S227* | Primary ovarian insufficiency | Colombo et al. (2017)† | 3.98E-06 | 8.24E-06 | |||
| STAG3 | NM_012447.2:c.1573+5G>A | p.L490Tfs*10 | Primary ovarian insufficiency | He et al. (2018) | 1.19E-05 | 3.19E-05 | |||
| STAG3 | NM_012447.3:c.1947_1948dup | p.Y650Sfs*22 | Primary ovarian insufficiency | Le Quesne Stabej et al. (2016) | NR | ||||
| STAG3 | NC_000007.13:g.99786485del | p.F187fs*7 | Primary ovarian insufficiency | Caburet et al. (2014) | NR | ||||
| STAG3 | NM_001282716.1:c.659T > G | p.L220R | Primary ovarian insufficiency | Heddar et al. (2019) | NR | ||||
| NM_001282716.1:c.3052del | p.R1018DfsTer14 | NR | |||||||
| STAG3 | NC_000007.13:g.99794799G>A | p.R321H | Primary ovarian insufficiency | Jaillard et al. (2020) | NR | ||||
| MCM8 | NC_000020.10:g.5948227G>A | p.E341K | Early menopause risk | He et al. (2009) | 0.0451 | 0.0451 | 0.0378 | ||
| MCM8 | NC_000020.10:g.5948227G>A | p.E341K | Early menopause risk | Murray et al. (2011) | 0.0378 | 0.0451 | 0.0451 | ||
| MCM8 | NC_000020.10:g.5948227G>A | p.E341K | Early menopause risk | Chen et al. (2011) | 0.0451 | 0.0451 | 0.0378 | ||
| MCM8 | NC_000020.11:g.5954739T>A | Intronic variant | Early menopause risk | Chen et al. (2012) | NR | ||||
| MCM8 | NM_001281520.1:c.1954–1G>A | p.V652Wfs*6, p.V652_Q664del, or p.V652_E721del | Primary ovarian insufficiency | Tenenbaum-Rakover et al. (2015) | 3.98E-06 | 8.25E-06 | |||
| MCM8 | NM_001281520.1:c.1469_1470insTA | p.L491Ifs*88 | Primary ovarian insufficiency | Tenenbaum-Rakover et al. (2015) | NR | ||||
| MCM8 | NM_032485:c.446C>G | p.P149R | Primary ovarian insufficiency | AlAsiri et al. (2015)† | NR | ||||
| MCM8 | NM_001281520.1:c.482A>C | p.H161P | Primary ovarian insufficiency | Bouali et al. (2017) | NR | ||||
| MCM8 | NC_000020.10:g.5948227G>A | p.E341K | Early menopause risk | Coignet et al. (2017) | 0.0451 | 0.0451 | 0.0378 | ||
| MCM8 | NC_000020.11:g.5954739T>A | Intronic variant | Early menopause risk | Coignet et al. (2017) | NR | ||||
| MCM8 | NM_001281522.1:c.925C>T | p.R309* | Growth retardation, recurrent pilomatricomas, and primary amenorrhea | Heddar et al. (2020) | 7.96E-06 | 8.24E-06 | |||
| MCM8 | NM_032485.4:c.351_354del | p.K118Efs*5 | Primary ovarian insufficiency | Zhang et al. (2020a) | NR | ||||
| MCM9 | NM_017696.2:c.1732+2T>C | Splice donor site variant | Primary ovarian insufficiency and short stature | Wood-Trageser et al. (2014) | 1.33E-05 | ||||
| MCM9 | NM_017696.2:c.394C>T | p.R132* | Primary ovarian insufficiency and short stature | Wood-Trageser et al. (2014) | 7.97E-06 | 8.24E-06 | |||
| MCM9 | NC_000006.11:c.672_673delinsC | p.Q225Kfs*4 | Primary ovarian insufficiency; mixed polyposis and colorectal cancer | Goldberg et al. (2015)† | NR | ||||
| MCM9 | NM_017696.2:c.1483G>T | p.E495* | Primary ovarian insufficiency and short stature | Fauchereau et al. (2016) | NR | ||||
| DMC1 | NM_007068.3: c.106G>A | p.D36N | Primary ovarian insufficiency | He et al. (2020b) | NR | ||||
| PSMC3IP | NM_016556.2:c.600_602del | p.E201del | 46,XX ovarian dysgenesis | Zangen et al. (2011) | NR | ||||
| PSMC3IP | NC_000017.10:c.489C>G | p.Y163* | Primary ovarian insufficiency | Al-Agha et al. (2018)† | NR | ||||
| PSMC3IP | NM_016556:c.496_497del | p.R166Afs | Primary ovarian insufficiency | Yang et al. (2019)† | NR | ||||
| PSMC3IP | NM_016556:c.430_431insGA | p.L144* | Primary ovarian insufficiency | Yang et al. (2019)† | NR | ||||
†
Reference sequence or reference sequence version number not reported
1
Frequency in gnomAD v.2.1.1 exomes
2
Frequency in ExAc v1.0
3
Frequency in gnomAD SVs v2.1
4
Frequency in gnomAD v2.1.1 genomes
NR, not reported