Table 3.
Homozygous Finnish enriched variants observed ≥2 times across NFID and the Southern and Northern Finnish NDD cases and not observed in any controls as homozygous
| Variant | Gene | Previous evidence | GnomAD Finnish AF | GnomAD pop. Max AF | NFID AF | RAFT meta p | NFID case homs | NFID RAFT p | Population NDD case homs | Population NDD RAFT p |
|---|---|---|---|---|---|---|---|---|---|---|
| 12:94243956 G:A (mis) | CRADD | AR Lissencephaly, ID25 | 6.01E−3 | 9.15E−4 | 7.83E−3 | 5.01E−8 a | 3 | 1.86E−6 | 1 | 9.30E−3 |
| 7:81374424 G:C (mis) | HGF | AR hearing loss (OMIM) | 1.12E−3 | 5.48E−4 | 2.52E−3 | 1.34E−5 a | 1 | 3.20E−3 | 1 | 2.54E−3 |
| 12:15784582 T:C (mis) | EPS8 | AR deafness (OMIM) Cognition defects in mice51 | 9.03E−3 | 1.30E−3 | 6.89E−3 | 1.28E−4 | 2 | 1.28E−4 | 0 | NA |
| 1:220236134 C:T (mis) | BPNT1 | - | 1.07E−2 | 4.83E−3 | 6.89E−3 | 1.34E−4 | 2 | 1.34E−4 | 0 | NA |
| 7:1520077 T:C (mis) | INTS1 | AR ID26 | 1.30E−2 | 3.05E−3 | 1.71E−2 | 1.95E−4 | 3 | 1.95E−4 | 0 | NA |
| 2:95753239 A:G (mis) | MRPS5 | - | 9.87E−3 | 4.56E−3 | 8.29E−3 | 2.88E−4 | 2 | 2.88E−4 | 0 | NA |
| 10:123844296 C:A (mis) | TACC2 | - | 1.32E−2 | 1.10E−3 | 1.14E−2 | 1.05E−3 | 2 | 1.05E−3 | 0 | NA |
| 1:155028692 C:T (mis) | ADAM15 | - | 8.69E−3 | 2.37E−3 | 1.18E−2 | 2.11E−3 | 1 | 4.84E−2 | 1 | 3.58E−2 |
| 18:14542688 G:A (mis) | POTEC | - | 1.86E−2 | 6.26E−3 | 1.98E−2 | 2.11E−3 | 2 | 1.01E−2 | 1 | 1.65E−1 |
| 21:19651329 G:C (mis) | TMPRSS15 | Enterokinase deficiency (OMIM) | 1.73E−2 | 6.31E−3 | 1.93E−2 | 2.66E−3 | 1 | 1.42E−1 | 2 | 9.85E−3 |
| 15:60789800 T:C (mis) | RORA | AD ID52 | 1.02E−2 | 9.14E−4 | 1.59E−2 | 4.03E−3 | 1 | 9.35E−2 | 1 | 3.38E−2 |
| 11:6023849 C:T (mis) | OR56A4 | - | 1.69E−2 | 1.82E−3 | 1.61E−2 | 4.45E−3 | 2 | 4.45E−3 | 0 | NA |
| 11:3681309 G:A (mis) | ART1 | - | 1.64E−2 | 3.68E−3 | 1.53E−2 | 5.67E−3 | 1 | 8.43E−2 | 1 | 5.76E−2 |
| 19:56424477 TC:T (frameshift) | NLRP13 | - | 1.65E−2 | 1.28E−3 | 1.40E−2 | 6.07E−3 | 1 | 7.44E−2 | 1 | 8.54E−2 |
| 8:17612739 G:C (mis) | MTUS1 | - | 1.46E−2 | 2.01E−3 | 1.54E−2 | 6.74E−3 | 1 | 9.22E−2 | 1 | 7.45E−2 |
| 1:183520048 A:T (mis) | SMG7 | NMD-components linked to ID53 | 2.49E−2 | 1.10E−3 | 2.62E−2 | 3.85E−2 | 1 | 2.85E−1 | 1 | 1.58E−1 |
| X:23410887 C:T (mis) | PTCHD1 | x-linked ID/AUTISM54 | 2.43E−4 | 2.51E−5 | 2.27E−4 | NA | 1b | NA | 1b | NAb |
AR autosomal recessive, AD autosomal dominant, ID intellectual disability, AF allele frequency, mis missense
aSignificant after multiple testing correction
bRAFT statistic not valid for X-chromosome. Both carriers are hemizygote males