Table 1. Scoring scheme for variant evaluation (adapted from Hertz et al. 31 ).
| Parameter | Score |
|---|---|
| Coding effect | |
| Nonsense | 24 |
| Frameshift | 24 |
| Splice sites | |
| ±1/±5 | 24 |
| ±2/±3 | 12 |
| All others | 0 |
| Missense | 0 |
| In silico protein prediction | |
| AGVGD | |
| C65 | 4 |
| C55 | 3.2 |
| C35 | 2.4 |
| C25 | 1.6 |
| C15 | 0.8 |
| C0 | 0 |
| NA | 0 |
| Grantham distance | |
| >140 | 4 |
| 70–140 | 2 |
| <70 | 0 |
| NA | 0 |
| SIFT | |
| Deleterious | 4 |
| Good | 0 |
| NA | 0 |
| MAPP | |
| Bad | 4 |
| Good | 0 |
| NA | 0 |
| Polyphen2 | |
| Probably damaging | 4 |
| Possibly damaging | 2 |
| Benign | 0 |
| MutationTaster | |
| Disease causing | 4 |
| Polymorphism | 0 |
| NA | 0 |
| MAF | |
| ESP EAMAF | |
| ≤0.001 | 8 |
| 0.001<freq≤0.002 | 5.3 |
| 0.002<freq≤0.01 | 2.6 |
| >0.01 | 0 |
| NA | 0 |
| ExAC EURNFMAF | |
| ≤0.001 | 8 |
| 0.001<freq≤0.002 | 5.3 |
| 0.002<freq≤0.01 | 2.6 |
| >0.01 | 0 |
| NA | 0 |
| 1000 Genomes Project EURMAF | |
| ≤0.001 | 8 |
| 0.001<freq≤0.002 | 5.3 |
| 0.002<freq≤0.01 | 2.6 |
| >0.01 | 0 |
| NA | 0 |
Abbreviations: AGVGD, align Grantham variation and Grantham deviation32; ESP EAMAF, MAF in European American population in NHLBI GO Exome Sequencing Project37; ExAC EURNFMAF, MAF in European (non-Finnish) population in exome aggregation consortium39; MAF, minor allele frequency; MAPP, multivariate analysis of protein polymorphism prediction34; NA, not available; Polyphen2, polymorphism phenotyping v2 (ref. 35); SIFT, sorting intolerant from tolerant prediction33; MutationTaster36; 1000 Genomes Project EURMAF, MAF in European population in 1000 Genomes Project.38