Table II.
In silico analysis of sequence variants demonstrated by whole-exome sequencing in the embryos from cases of missed abortion.
| Embryo ID | Gene | Reference mRNA no. | Mutation type | Variants | Aa change | Polyphen-2 | SIFT | Mutation Taster | FATHMM-MKL | M Z score | pLI | HI, % |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| QW001 | LIAS | NM_006859 | m | c.991T>C | p.W331R | D (0.997) | D (0) | D (1.0) | D (0.976) | 1.16 | 0.06 | 12.37 |
| QW002 | PADI6 | NM_207421 | m | c.122C>T | p.A41V | P (0.892) | N.A. | N.A. | N (0.422) | N.A. | N.A. | N.A. |
| QW004 | ATE1 | NM_007041 | m | c.929G>A | p.C310Y | P (0.855) | D (0.016) | D (1.0) | D (0.985) | −0.13 | 0.51 | 45.89 |
| QW005 | INTS1 | NM_001080453 | m | c.3934C>A | p.L1312M | B (0.183) | T (0.174) | D (0.82) | D (0.896) | 1.18 | 0.22 | 52.90 |
| PIKFYVE | NM_015040 | m | c.3683A>T | p.Q1228L | D (0.987) | T (0.245) | D (1.0) | D (0.989) | 1.58 | 0.98 | 20.31 | |
| RAC1 | NM_018890 | m | c.230G>C | p.G77A | D (0.992) | T (0.137) | D (0.997) | D (0.962) | 3.42 | 0.57 | 0.72 | |
| SCARB1 | NM_005505 | m | c.20C>A | p.A7E | D (0.997) | D (0.032) | N (1.0) | N (0.172) | 1.83 | 0.08 | 37.77 | |
| QW007 | OTX2 | NM_172337 | m | c.475C>A | p.P159T | D (0.999) | D (0.002) | D (1.0) | D (0.985) | 1.02 | 0.74 | 0.71 |
| QW008 | BPTF | NM_182641 | m | c.2882T>A | p.I961K | B (0.017) | D (0.002) | D (0.999) | D (0.912) | 4.39 | 1.00 | 36.79 |
| CREBBP | NM_004380 | m | c.3107C>A | p.T1036K | B (0.008) | T (0.527) | D (0.981) | D (0.908) | 5.58 | 1.00 | 0.62 | |
| HSF1 | NM_005526 | m | c.1462C>G | p.L488V | P (0.798) | D (0.007) | D (0.993) | D (0.938) | 0.54 | 0.59 | 48.62 | |
| NF1 | NM_000267 | m | c.1648C>A | p.L550M | D (1.0) | T (0.092) | D (0.999) | D (0.899) | 6.22 | 1.00 | 0.87 | |
| PIKFYVE | NM_015040 | m | c.3307A>G | p.K1103E | D (0.997) | T (0.222) | D (1.0) | D (0.998) | 1.58 | 0.98 | 20.31 | |
| PTCH1 | NM_000264 | m | c.3470C>A | p.A1157E | D (0.973) | T (0.071) | D (1.0) | D (0.991) | 2.86 | 1.00 | 0.48 | |
| RAPGEF2 | NM_014247 | m | c.3203T>A | p.V1068E | B (0.243) | T (0.319) | D (1.0) | D (0.993) | 3.22 | 1.00 | 21.18 | |
| QW010 | RGS14 | NM_006480 | m | c.510C>G | p.S170R | D (1.0) | D (0) | D (1.0) | D (0.916) | 1.15 | 0.02 | 61.07 |
| TRIM28 | NM_005762 | m | c.361A>C | p.K121Q | D (0.997) | T (0.172) | D (1.0) | D (0.604) | 3.16 | 1.00 | 27.80 | |
| QW011 | PTPRB | NM_001109754 | m | c.5561T>C | p.V1854A | B (0.002) | D (0.034) | N (0.97) | D (0.838) | 0.49 | 0.94 | 39.33 |
| QW012 | DIDO1 | NM_033081 | m | c.3064C>T | p.P1022S | P (0.759) | T (0.177) | D (0.929) | D (0.963) | 3.10 | 1.00 | 83.16 |
| KIF16B | NM_001199866 | m | c.3802G>T | p.V1268F | B (0.007) | D (0) | D (0.864) | N (0.096) | 0.69 | 0.00 | 44.93 | |
| ZNF568 | NM_198539 | s | c.514A>T | p.R172X | N.A. | N.A. | D (1.0) | N (0.066) | 0.27 | 0.00 | 88.58 | |
| QW013 | FAM208A | NM_015224 | m | c.1616A>G | p.H539R | D (0.991) | T (0.177) | D (1.0) | D (0.883) | 0.89 | 1.00 | 29.50 |
| KAT2A | NM_021078 | m | c.671C>A | p.P224H | D (1.0) | D (0) | D (1.0) | D (0.98) | 4.79 | 0.41 | 22.83 | |
| KDM1A | NM_015013 | m | c.1759A>T | p.N587Y | D (1.0) | T (0.051) | D (1.0) | D (0.991) | 5.56 | 0.99 | 5.56 | |
| LDB1 | NM_003893 | m | c.662C>T | p.S221L | D (0.985) | D (0.001) | D (1.0) | D (0.977) | 3.24 | 0.88 | 2.24 | |
| NOTCH1 | NM_017617 | m | c.2953C>G | p.P985A | D (0.969) | T (0.352) | D (1.0) | D (0.966) | 4.48 | 1.00 | 0.15 | |
| POGLUT1 | NM_152305 | m | c.832T>G | p.F278V | D (1.0) | D (0.001) | D (1.0) | D (0.937) | 1.08 | 0.00 | 20.35 | |
| QW014 | CDH5 | NM_001795 | s | c.1138C>T | p.Q380X | N.A. | N.A. | A (1.0) | D (0.736) | 0.02 | 0.15 | 32.63 |
| GAS1 | NM_002048 | m | c.610C>T | p.R204C | D (1.0) | D (0.002) | D (1.0) | D (0.772) | 4.27 | 0.62 | 29.14 | |
| QW015 | DLX3 | NM_005220 | m | c.314C>T | p.A105V | B (0.037) | T (0.119) | D (0.987) | D (0.918) | 1.87 | 0.01 | 40.57 |
| PTPRB | NM_001109754 | m | c.359T>C | p.V120A | B (0.39) | D (0.007) | N (1.0) | D (0.788) | 0.49 | 0.94 | 39.33 | |
| QW016 | INTS1 | NM_001080453 | m | c.6475C>T | p.L2159F | D (0.999) | D (0.006) | D (1.0) | D (0.963) | 1.18 | 0.22 | 52.90 |
| SALL4 | NM_020436 | m | c.733C>A | p.H245N | B (0.067) | T (0.16) | D (1.0) | D (0.865) | 1.66 | 1.00 | 38.00 | |
| QW018 | SRRT | NM_015908 | m | c.1148A>C | p.K383T | D (0.999) | T (0.249) | D (1.0) | D (0.987) | 4.61 | 0.98 | 30.36 |
| VPS26A | NM_004896 | m | c.758C>T | p.A253V | B (0.388) | D (0.019) | D (1.0) | D (0.996) | 0.94 | 0.66 | 11.04 | |
| QW019 | CREBBP | NM_004380 | m | c.2917C>A | p.P973T | P (0.952) | T (0.055) | D (1.0) | D (0.992) | 5.58 | 1.00 | 0.62 |
Polyphen-2 prediction scores range from 0 to 1 with high scores indicating probably or possibly damaging. D, probably damaging; P, possibly damaging; B, benign; N.A., not available. SIFT scores vary between 0 and 1. Variants with scores close or equal to 0 are predicted to be damaging. D, Damaging; T, tolerated; N.A., not available. Mutation Taster: The probability value is the probability of the prediction, i.e., a value close to 1 indicates a high ‘security’ of the prediction. D, probably deleterious; N, polymorphism; A, known to be deleterious. FATHMM-MKL values >0.5 are predicted to be deleterious, while those <0.5 are predicted to be neutral or benign. D, deleterious; N, neutral; M Z score, missense Z score: Positive Z scores indicate increased constraint (intolerance to variation) and therefore that the gene had fewer variants than expected. Negative Z scores are given to genes that exhibit more variants than expected. pLI: The closer pLI is to one, the more LoF-intolerant the gene appears to be. pLI >= 0.9 was considered as an extremely LoF intolerant set of genes. HI, high ranks (e.g. 0–10%) indicate a gene is more likely to exhibit HI; low ranks (e.g., 90–100%) indicate a gene is more likely to not exhibit HI. m, missense; s, stopgain; Aa, amino acid; LoF, loss of function; HI, haploinsifficiency; pLI, loss intolerance.