Table 3.
Likely Gene-Disrupting (LGD) Mutations in Affected Children
| Family ID | Gender | Variant | Effect | Gene | Amino Acid Position | FMRP Target |
|---|---|---|---|---|---|---|
| 12221 | M | sub(C →T) | N | FAM91A1 | 72/839 | Yes |
| 12501 | M | sub(A →T) | N | NRXN1 | 587/1,177 | Yes |
| 12645 | M | sub(C →T) | N | ANK2 | 104/1,049 | Yes |
| 12764 | F | sub(C →A) | N | NCKAP1 | 1,082/1,129 | Yes |
| 12840 | M | sub(C→T) | N | ATP1B1 | 143/299 | Yes |
| 12867 | F | sub(G →A) | N | TRIP12 | 35/1,723 | Yes |
| 13094 | M | sub(T→A) | N | WDFY3 | 978/3,527 | Yes |
| 12683 | M | del(1) | F | KDM6B | 192/1,683 | Yes |
| 12705 | M | ins(C) | F | DIP2C | 657/1,557 | Yes |
| 12952 | M | del(1) | F | MLL5 | 1,066/1,859 | Yes |
| 13012 | M | ins(CTGGTCT) | F | DIP2A | 608/1,568 | Yes |
| 13092 | M | ins(AGGTCAG) | F | LMTK3 | 307/1,490 | Yes |
| 13612 | M | del(4) | F | DST | 3,268/5,172 | Yes |
| 12969 | M | ins(C) | S | MED13L | 1,789/2,211 | Yes |
| 12409 | M | sub(G →A) | N | LRP2 | 3,184/4,656 | No |
| 12463 | M | sub(C →T) | N | UNC80 | 518/1,765 | No |
| 12653 | M | sub(C →T) | N | KIAA0232 | 118/1,396 | No |
| 12669 | M | sub(C →T) | S | RABGGTA | UTR | No |
| 12792 | M | sub(C →T) | N | ANO5 | 420/913 | No |
| 12840 | M | sub(C →T) | S | TM4SF19 | 68/210 | No |
| 12864 | F | sub(C →T) | S | SUV420H1 | 86/646 | No |
| 13010 | M | sub(G →C) | S | TBC1D23 | 293/700 | No |
| 13042 | M | sub(G →A) | N | THSD7A | 879/1,658 | No |
| 13125 | M | sub(C →T) | N | RAD21L1 | 54/557 | No |
| 13197 | M | sub(G →T) | N | NR3C2 | 701/868 | No |
| 13234 | M | sub(G →A) | N | CBX4 | 131/561 | No |
| 13349 | M | sub(G →A) | N | NUAK1 | 433/662 | No |
| 13364 | M | sub(G →A) | N | ECM2 | 182/678 | No |
| 13506 | M | sub(C →A) | N | SCUBE2 | 80/1,000 | No |
| 13513 | M | sub(G →A) | S | ZMYND11 | 239/455 | No |
| 13526 | M | sub(A /G) | S | CACNA2D3 | 592/939 | No |
| 13670 | F | sub(C →T) | N | NFIA | 30/502 | No |
| 12323 | M | del(1) | F | PHF2 | 1,088/1,097 | No |
| 12652 | M | del(1) | F | SPATA13 | 127/1,278 | No |
| 12653 | M | ins(A) | F | DLL1 | 431/724 | No |
| 12773 | M | del(4) | F | PCDHA13 | 678/951 | No |
| 12826 | F | del(4) | F | TROVE2 | 253/539 | No |
| 12858 | F | del(1) | F | PAX5 | 111/392 | No |
| 12939 | M | del(2) | F | SLC25A39 | 104/352 | No |
| 12950 | M | del(4) | F | UBN2 | 1,063/1,348 | No |
| 13018 | M | del(1) | F | PCOLCE | 101/450 | No |
| 13070 | M | del(2) | F | CTTNBP2 | 760/1,664 | No |
| 13096 | M | del(1) | F | GIMAP8 | 149/666 | No |
| 13162 | M | ins(A) | F | RIMS1 | 196/1,693 | No |
| 13168 | F | del(1) | F | MFRP | 342/580 | No |
| 13176 | F | del(1) | F | ZFYVE26 | 397/2,540 | No |
| 13183 | M | ins(G) | F | BCL11A | 265/836 | No |
| 13398 | M | ins(CGTCATCA) | F | POGZ | 1,108/1,316 | No |
| 13439 | M | ins(A) | F | CSTF2T | 354/617 | No |
| 13471 | M | del(2) | F | FLG | 147/4,062 | No |
| 13537 | M | del(4) | S | TUBGCP4 | 578/667 | No |
| 13548 | F | del(1) | F | GALNTL4 | 521/608 | No |
| 13552 | M | del(1) | F | DYRK1A | 487/755 | No |
| 13585 | M | ins(G) | F | ACACB | 114/2,459 | No |
| 13586 | M | ins(G) | F | TRIM17 | 274/478 | No |
| 13590 | M | ins(A) | F | MTHFS | 147/147 | No |
| 13590 | M | del(1) | F | EFCAB5 | 848/857 | No |
| 13616 | M | ins(G) | F | ATP10D | 1,001/1,427 | No |
| 13646 | M | del(5) | F | VCP | 515/807 | No |
SNV and indel variants from affected children that are likely to disrupt the function of the corresponding proteins are listed. The “family ID” column indicates the SSC ID of the relevant family. Under “gender,”Mstands for males and F for females. The “variant” column shows detail for reconstructing the haplotype around the de novo variant relative to the reference genome as follows: “sub(R/A)” represents a substitution of the reference allele to an alternative allele; “ins(seq)” indicates an insertion of the provided sequence “seq” and “del(N)” denotes a deletion of N nucleotides. Chromosomal locations for events can be found in Table S2. Under “effect,” “N” stands for nonsense, “S” for splice site, and “F” for frame shift events. The “amino acid position” column shows the position of the first incorrectly encoded amino acid (or nonsense codon) within the encoded protein/the length of the protein. When a mutation affects multiple isoforms of a transcript, the earliest proportionate coordinate is given. “FMRP target” indicates whether the corresponding gene’s RNA was found to physically associate with FMRP (Darnell et al., 2011). See “Recurrence and Overlaps with FMRP-Associated Genes” in the Results as well as Tables 5 and 6 for additional details.