Table 4. Properties and potential functional effects of missense and frameshift mutations.
| Annotationa | Novel? | OR (95% CI)c | NT conservationd | Splicing analysise | AA conservationf | Interpretationg | ||
| GERP | Predicted effect(# predictions/# matrices) | SIFT | Polyphen | Panther | ||||
| ATF5 | ||||||||
| R167C | Y | 2.61 (0.5–13.4) | 0 | ++ | (++) | + | Possible amino acid effect | |
| DISC1 | ||||||||
| A83V | 1.51 (0.75–3.01) | + | new splice site [−801 nt] (2/2) | + | − | − | Possible splicing effect | |
| W160L | Y | 2.09 (0.52–8.37) | 0 | − | − | − | No obvious functional effect | |
| R264Q | 1.01 (0.83–1.22) | − | new splice site [−725 nt] (2/2) | − | − | − | Possible splicing effect | |
| L607F | 0.89 (0.7–1.12) | + | + | − | + | Possible amino acid effect | ||
| S704C | 1.01 (0.83–1.23) | + | + | + | + | Possible amino acid effect | ||
| E751Q b | 1.83 (0.76–4.37) | + | + | − | − | No obvious functional effect (though genomically conserved) | ||
| FEZ1 | ||||||||
| D123E | 1.09 (0.86–1.37) | 0 | − | − | − | No obvious functional effect(though genomically conserved) | ||
| E358Q | Y | 0.64 (0.29–1.35) | + | ESE site broken (8/4) | − | − | − | Possible splicing effect |
| NDE1 | ||||||||
| T191I | Y | 0.89 (0.41–1.94) | + | − | − | − | No obvious functional effect (though genomically conserved) | |
| NDEL1 | ||||||||
| P342S | Y | 0.00 (0.00-NaN) | + | (+) | (++) | NM | Uninterpretable* | |
| PDE4B | ||||||||
| A112G | Y | 1.76 (0.63–4.86) | + | − | − | NM | No obvious functional effect (though genomically conserved) | |
| TRAF3IP1 | ||||||||
| R139Q | Y | 0.60 (0.14–2.55) | 0 | − | − | NM | No obvious functional effect | |
| N228S | 0.96 (0.61–1.5) | − | − | − | NM | No obvious functional effect | ||
| E260K | Y | 2.08 (0.19–23.03) | + | − | − | NM | No obvious functional effect (though genomically conserved) | |
| K295N | 1.05 (0.86–1.27) | 0 | ESE site broken (13/4) | (+) | − | NM | Possible splicing effect * | |
| D400A | Inf (NaN-Inf) | + | (−) | (++) | NM | No obvious functional effect (though genomically conserved)* | ||
| T416S | Y | 0.96 (0.62–1.5) | 0 | (−) | − | NM | Uninterpretable* | |
| M620L | 0.71 (0.36–1.43) | + | − | − | NM | No obvious functional effect (though genomically conserved) | ||
| V682X | Y | 1.00 (0.06–16.13) | + | NA | NA | NA | Possible functional effect (premature stop codon) | |
| ZNF365 | ||||||||
| P26L | Y | 3.15 (0.32–30.2) | 0 | (+) | − | − | No obvious functional effect | |
| A62T | 0.95 (0.78–1.16) | − | (−) | − | − | No obvious functional effect | ||
| S337A | 0.86 (0.71–1.02) | 0 | − | − | − | No obvious functional effect | ||
Rare mutations (MAF<1%) are underlined.
Rare allele, also reported by Song and colleagues74.
OR>1.5 or <0.67 are shown in bold.
GERP: -, divergent (score <−1); +, conserved (score >1); 0, intermediate (−1< score <1).
Only splicing predictions based on >1 matrix, and located <30 nt from the nearest exon-intron boundary were considered. For predicted splice sites, exon length variation associated with the use of the cryptic site is indicated between square brackets.
SIFT: -, tolerated; + possibly damaging; ++, damaging. PolyPhen: -, benign; +, possibly damaging; ++, probably damaging. Panther: -, unlikely functional effect (pdeleterious <0.5); +, possibly damaging (0.5 < pdeleterious <0.75); NM, not modeled by the algorithm.
AA conservation predictions in parenthesis are based on less than 6 sequences in the alignment, and should be interpreted with caution.
NA: not applicable.
Interpretations were made irrespective of the observed odds ratios.
*more sequence data needed to allow more reliable predictions to be made on the amino acid level.