Table 2.
Potentially pathogenic variants in novel candidate ASD genes identified in affected individuals from the East African ASD cohort
| Affected individual | Inheritance | Variant(s) | Variant type | Gene(s) | Variant location | Mutation | pLI score | LOEUF score |
|---|---|---|---|---|---|---|---|---|
| MC-35-3 | compound heterozygous | chr1:3,329,057:G:A; chr1:3,331,149:G:T | missense | PRDM16 | exonic | p.G766S; p.D877Y | 1 | 0.19 |
| MC-35-3 | X-linked | chrX:9,863,880:C:G | missense | SHROOM2 | exonic | p.S644R | 0 | 0.53 |
| MCD-01-3 | inherited homozygous (ROH) | chr11:27,743,920:C:A | SNV | BDNF | promoter | – | 0.66 | 1.52 |
| MCD-02-3 | X-linked | chrX:112,022,894:C:T | missense | AMOT | exonic | p.G830R | 1 | 0.27 |
| MCD-02-3 | X-linked | chrX:153,051,602:GGCTACAGGA:- | Frameshift | IDH3G | exonic | p.L379Pfs∗91 | 0.09 | 0.71 |
| MCD-04-5 | compound heterozygous | chr2:108,924,874:G:C; chr2:108,910,151:C:T | missense; Stop gain | SULT1C2 | exonic | p.R282T; p.Q10X | 0 | 1.34 |
| MCD-04-5 | X-linked | chrX:67,731,809:G:A | missense | YIPF6 | exonic | p.R59H | 0.90 | 0.41 |
| MCD-05-3 | compound heterozygous | chr11:92,577,302:C:T; chr11:92,533,549:G:A | missense | FAT3 | exonic | p.S3590L; p.R2457Q | 1 | 0.25 |
| MCD-06-3∗ | inheritedhomozygous (ROH) | chr15:79,143,366:A:T | SNV | ADAMTS7, MORF4L1, CTSH | enhancer | – | 0; 0.99; 0 | 0.65; 0.27; 1.01 |
| MCD-07-3 | inherited homozygous (ROH) | chr10:16,392,185:G:A | SNV | MINDY3, PTER | enhancer | – | 0.01; 0 | 0.054; 1.82 |
| MCD-07-3 | inherited homozygous (ROH) | chr16:1,040,862:G:A | SNV | SOX8, SSTR5-AS1, SSTR5 | enhancer | – | 0.67; –; 0 | 0.51; –; 1.59 |
| MCD-08-3∗ | inherited homozygous (ROH) | chr6:96,506,344:-:AAAAA | Indel | FUT9, MANEA, UFL1 | enhancer | – | 0.08; 0; 0 | 0.71; 0.86; 0.84 |
| MCD-10-3 | compound heterozygous | chr3:97,686,151:T:C; chr3:97,677,992:T:C | missense | RIOX2 | exonic | p.Y96C; p.H195R | 0 | 1.07 |
| MCD-11-3 | inherited homozygous (ROH) | chr4:15,937,843:A:G | missense | FGFBP1 | exonic | p.V138A | 0.59 | 1.06 |
| MCD-11-3 | X-linked | chrX:101,909,395:A:G | missense | GPRASP1 | exonic | p.E185G | 0.31 | 0.42 |
| MCD-13-3 | compound heterozygous | chr6:75,893,146:A:G; chr6:75,838,134:A:G | missense | COL12A1 | exonic | p.I504T; p.V2073A | 0.97 | 0.28 |
| MCD-13-3 | compound heterozygous | chr15:59,373,446:A:G; chr15:59,359,263:G:C | missense | RNF111 | exonic | p.M754V; p.G556A | 1 | 0.21 |
| MCD-14-3∗ | X-linked | chrX:9,693,868:C:T | missense | GPR143 | exonic | p.S378N | 0.93 | 0.37 |
| MCD-14-3∗ | X-linked | chrX:153,035,691:C:T | missense | PLXNB3 | exonic | p.P592S | 0.23 | 0.37 |
| MCD-14-3∗ | De novo | chr8:144,688,700:A:T | stop gain | PYCR3 | exonic | p.C154X | 0 | 1.43 |
| MCD-15-3 | compound heterozygous | chr22:50,315,388:G:A; chr22:50,315,966:C:G | missense | CRELD2 | exonic | p.E191K; p.S205C | 0 | 1.05 |
| MCD-15-3 | X-linked | chrX:71,873,343:A:G | missense | PHKA1 | exonic | p.I360T | 0 | 0.55 |
| MCD-16-3 | X-linked | chrX:110,491,920:C:T | missense | CAPN6 | exonic | p.R454H | 0.82 | 0.39 |
| MCD-16-3 | De novo | chr5:31,317,594:A:T | missense | CDH6 | exonic | p.N542I | 0.92 | 0.34 |
| MCD-16-3 | X-linked | chrX:83,128,919:G:T | missense | CYLC1 | exonic | p.K401N | 0.93 | 0.37 |
| MCD-16-3 | compound heterozygous | chr13:76,414,552:C:T; chr13:76,409,449:G:T | missense | LMO7 | exonic | p.P935L; p.D870Y | 0 | 0.41 |
| MCD-17-3 | X-linked | chrX:120,182,861:GT:. | frameshift | GLUD2 | exonic | p.W442Afs∗16 | 0.03 | 1.27 |
| MCD-17-3 | inherited homozygous (ROH) | chr10:25,463,474:G:C | SNV | GPR158-AS1 | promoter | – | – | – |
| MCD-17-3 | X-linked | chrX:17,820,025:C:T | missense | RAI2 | exonic | p.E36K | 0.61 | 0.66 |
| MCD-17-3 | X-linked | chrX:153,714,877:T:C | missense | UBL4A | exonic | p.Q16R | 0.30 | 1.18 |
| MCD-18-3 | compound heterozygous | chr5:74,364,457:G:A; chr5:74,532,495:T:- | missense; Frameshift | ANKRD31 | exonic | p.R1837C; p.Q6Rfs∗10 | 0 | 0.87 |
| MCD-18-3 | X-linked | chrX:149,680,360:C:T | missense | MAMLD1 | exonic | p.L672F | 0.63 | 0.45 |
| MCD-18-3 | compound heterozygous | chr12:110,943,480:C:T; chr12:110,952,911:C:T | missense | RAD9B | exonic | p.P59L; p.A110V | 0 | 1.37 |
| MCD-19-3 | compound heterozygous | chr2:209,210,794:A:G; chr2:209,190,942:C:G | missense | PIKFYVE | exonic | p.K1711R; p.T1136S | 0 | 0.39 |
| MCD-21-3 | compound heterozygous | chr3:111,603,790:A:G; chr3:111,603,963:T:A | missense | PHLDB2 | exonic | p.K289R; p.S347T | 0 | 0.59 |
| MCD-21-3 | inherited homozygous (ROH) | chr15:55,881,474:TTTTTG:- | indel | PYGO1 | promoter | – | 0.99 | 0.23 |
| MCD-22-3 | compound heterozygous | chr5:138,857,917:C:T; chr5:138,858,039:C:A | missense | TMEM173 | exonic | p.A233T; p.G192V | 0 | 0.90 |
| MCD-23-3 | inherited homozygous (ROH) | chr8:28,166,424:-:TGTGTGTGTGTGTGTGT | indel | ELP3, PNOC | enhancer | – | 0; 0.02 | 1.02; 1.10 |
| MCD-24-3 | compound heterozygous | chr3:52,555,908:G:A; chr3:52,557,482:G:A | missense | STAB1 | exonic | p.R2071H; p.A2394T | 0 | 0.81 |
| MCD-24-3 | compound heterozygous | chr15:54,792,341:C:T; chr15:54,919,033:G:A | missense | UNC13C | exonic | p.H1709Y; p.G2123R | 0 | 0.54 |
| MCD-24-3 | inherited homozygous (ROH) | chr20:62,406,258:G:A | SNV | ZBTB46 | promoter | – | 0.81 | 0.40 |
| MCD-25-3 | compound heterozygous | chr1:24,389,694:C:T; chr1:24,387,787:G:C | missense | MYOM3 | exonic | p.G1231E; p.A1316G | 0 | 1.11 |
| MCD-25-3 | inherited homozygous (ROH) | chr7:88,387,647:T:G; chr7:88,387,990:T:C; chr7:88,388,566:G:A | SNV | ZNF804B | promoter | – | 0 | 1 |
| MCD-26-3 | compound heterozygous | chr19:55,748,036:G:A; chr19:55,742,199:G:C | missense | PPP6R1 | exonic | p.R655C; p.P838R | 0.98 | 0.30 |
| MCD-27-3 | compoundheterozygous | chr15:68,609,616:C:T; chr15:68,624,693:C:T | missense | ITGA11 | exonic | p.R901Q; p.V517I | 0 | 0.55 |
| MCD-27-3 | inherited homozygous | chr11:74,570,283:C:T; chr11:74,638,465:C:T | missense | XRRA1 | exonic | p.V356M; p.V157M | 0 | 0.78 |
| MCD-28-3 | compound heterozygous | chr14:105,414,461:C:G; chr14:105,416,755:T:G | missense | AHNAK2 | exonic | p.E2343Q; p.E1578A | 0 | 1.01 |
| MCD-28-3 | inherited homozygous | chr4:101,331,507:G:A | missense | EMCN | exonic | p.H240Y | 0 | 0.96 |
| MCD-28-3 | compound heterozygous | chr20:20,493,587:C:A; chr20:20,552,253:G:A | missense | RALGAPA2 | exonic | p.V1476F; p.A1002V | 0 | 0.59 |
| MCD-29-3∗ | inherited homozygous (ROH) | chr8:132,048,583:C:T; chr8:132,052,935:G:C; chr8:132,053,736:C:T | SNV | ADCY8 | promoter | – | 0 | 0.54 |
| MCD-29-3∗ | inherited homozygous (ROH) | chr3:159,560,791:TTTTTTTTTTTTT:- | Indel | IQCJ-SCHIP1, SCHIP1 | promoter | – | 0.03; 0.99 | 0.53; 0.23 |
| MCD-30-3∗ | inherited homozygous (ROH) | chr11:66,190,893:T:G | SNV | NPAS4 | promoter | – | 0.97 | 0.32 |
| MCD-32-4 | X-linked | chrX:77,378,818:A:C | missense | PGK1 | exonic | p.N295H | 0.77 | 0.47 |
| MCD-32-4 | X-linked | chrX:131,205,199:G:A | missense | STK26 | exonic | p.A234T | 0.31 | 0.54 |
| MCD-32-4 | X-linked | chrX:37,931,320:G:C | missense | SYTL5 | exonic | p.G117A | 0 | 0.65 |
| MCD-33-3; MCD-33-4 |
compound heterozygous | chr12:58,220,823:C:T; chr12:58,220,841:C:T; chr12:58,220,831:C:G | missense | CTDSP2 | exonic | p.V104M; p.D98N; p.R101T | 0.11 | 0.67 |
List of deleterious coding and brain-specific regulatory noncoding variants affecting novel candidate ASD genes identified for each affected individual. ROH indicates inherited homozygous variants that are within runs of homozygosity. Indel, insertion or deletion; LOEUF, loss-of-function observed/expected upper bound fraction; SNV, single nucleotide variant. ∗ Samples with a missing parent sample where compound heterozygous variant calling was not possible and de novo, inherited homozygous, and X-linked variant calling relied on one parent only.