Table 1.
Predicted and observed effect of unselected de novo ENU mutations in 23 essential immune genes
| Gene symbol | Num hom tested | Mut phen obs? | UniProt identifier | AA change | Polyphen category | Polyphen score | SIFT cat. | GERP score* | Mut Assessor cat. | PANTH subPSEC† | Condel cat. | CADD Phred-like score‡ |
| Dclre1c | 3 | Yes | Q8K4J0 | L95Stop | ||||||||
| Dock8 | 1 | Yes | Q8C147 | R1630Stop | ||||||||
| Dock8 | 3 | Yes | Q8C147 | F1885Stop | ||||||||
| Ets1 | 4 | Yes | P27577 | P334L | Prob. Dam. | 1 | Del. | 3.97 | Medium | −2.3993 | Del. | 19.09 |
| Hnrnpl | 5 | No | Q8R081 | A118D | Prob. Dam. | 1 | Del. | 3.74 | Medium | −4.06474 | Del. | 22 |
| Tnfaip3 | 3 | No | Q60769 | F394S | Prob. Dam. | 1 | Del. | 3.27 | Medium | § | Del. | 16.78 |
| Satb1 | 2 | No | Q60611 | V99A | Prob. Dam. | 0.999 | Toler. | Low | −4.11365 | Neutral | 20.7 | |
| Btk | 3 | Yes | P35991 | Y152H | Prob. Dam. | 0.998 | Del. | 3.91 | Low | −2.39271 | Del. | 27 |
| Prkdc | 8 | No | P97313 | D382G | Prob. Dam. | 0.997 | Del. | 3.91 | Medium | −3.61416 | Del. | 23.6 |
| Il7r | 3 | Yes | P16872 | T56P | Prob. Dam. | 0.985 | Del. | 2.92 | Low | § | Del. | 12.47 |
| Lig4 | 4 | No | Q8BTF7 | Y335C | Prob. Dam. | 0.985 | Del. | 2.32 | § | 25.7 | ||
| Itch | 1 | No | Q8C863 | H563L | Prob. Dam. | 0.972 | Del. | 3.61 | Medium | −3.98029 | Del. | 21.5 |
| Tbx21 | 7 | No | Q9JKD8 | E481A | Prob. Dam. | 0.971 | Toler. | 3.22 | Low | −0.97263 | Neutral | 15.79 |
| Prkdc | 4 | No | P97313 | I1010T | Poss. Dam. | 0.935 | Del. | 3.17 | Medium | −1.55087 | Del. | 25.9 |
| Bcl2 | 3 | No | Q4VBF6 | T175A | Poss. Dam. | 0.924 | Toler. | 3.04 | Neutral | −2.00435 | Neutral | 14.68 |
| Dock8 | 5 | No | Q8C147 | N1567Y | Poss. Dam. | 0.904 | Del. | 3.66 | Medium | −4.15438 | Del. | 26 |
| Dock8 | 5 | No | Q8C147 | K26E | Poss. Dam. | 0.894 | Del. | 3.92 | Low | § | Del. | ¶ |
| Rag1 | 1 | Yes | P15919 | E803G | Poss. Dam. | 0.879 | Del. | 3.83 | High | −2.75501 | Del. | 29.2 |
| Il2ra | 2 | No | P01590 | V230A | Poss. Dam. | 0.763 | Del. | 1.89 | Low | −2.25488 | Del. | ¶ |
| Rasgrp1 | 4 | No | Q9Z1S3 | K659R | Poss. Dam. | 0.712 | Toler. | 3.49 | Low | −1.80793 | Neutral | 22.2 |
| Jak3 | 2 | No | Q62137 | I663V | Poss. Dam. | 0.705 | Del. | Low | −3.23261 | Del. | || | |
| Cd74 | 1 | No | P04441 | I203F | Poss. Dam. | 0.434 | Toler. | −2.02 | Medium | −2.04615 | Neutral | 17.91 |
| Prkdc | 5 | No | P97313 | V3389L | Benign | 0.346 | Toler. | 3.73 | Medium | § | Neutral | 21.5 |
| Ptprc | 3 | No | P06800 | K921R | Benign | 0.322 | Toler. | 2.64 | Low | −0.99775 | Neutral | 21.9 |
| Rag2 | 2 | No | P21784 | D424G | Benign | 0.151 | Toler. | 3.51 | Medium | −2.32166 | Neutral | ¶ |
| Prkdc | 2 | No | P97313 | Y2044F | Benign | 0.097 | Toler. | 3.35 | Medium | −2.36465 | Neutral | 13.5 |
| Tnfaip3 | 1 | No | Q60769 | K41E | Benign | 0.049 | Toler. | Neutral | −0.78466 | Neutral | 22.3 | |
| Ptpn6 | 4 | No | P29351 | D90E | Benign | 0.015 | Del. | −5.96 | Medium | § | Neutral | 12.48 |
| Lig4 | 1 | No | Q8BTF7 | N158K | Benign | 0.013 | Toler. | −0.667 | § | 15.95 | ||
| Prkdc | 3 | No | P97313 | V3589A | Benign | 0.007 | Toler. | −1.75 | Low | −1.69134 | Neutral | || |
| Dock8 | 4 | No | Q8C147 | T1748A | Benign | 0.001 | Toler. | 2.51 | Neutral | −1.77255 | Neutral | 14.89 |
| Cd22 | 1 | No | Q3UP36 | M157V | Benign | 0 | Toler. | 2.65 | Neutral | −0.93903 | Neutral | ¶ |
| Itpkb | 2 | No | B2RXC2 | L228P | Benign | 0 | Toler. | −1.04 | Neutral | § | Neutral | ¶ |
AA, amino acid; cat., category; Del., deleterious; Mut Assessor cat., MutationAssessor category; Mut phen obs?, mutant phenotype observed?; Num hom, number of homozygotes; Poss. Dam., possibly damaging; Prob. Dam., probably damaging; Toler., tolerated.
*
Larger GERP scores denote variants more likely to be deleterious.
†
Smaller subPSEC scores denote increasingly deleterious variants.
‡
Phred-like scores calculated using coordinates of mouse mutation lifted over to the orthologous human protein.
§
Missing values were not contained in the alignment created by the HMM.
¶
Mouse and human orthologs have a different amino acid at the variant site.
||
Absent in GRCh37.