Table 1.
ES filtering data obtained for the six consanguineous MMA probands
| Proband ID | Number of homozygous candidate variants | Variants in NOS3 (NM_000603) and GUCY1A3 (NM_000856.5) | ||
|---|---|---|---|---|
| Filter 1 | Filter 2 | Filter 3 | ||
| M030 | 8 | 6 | 3 | 0 |
| M035 | 21 | 18 | 11 | 1 homozygous missense substitution in NOS3 (c.1942 T > C, p.C648R) |
| M038 | 35 | 29 | 13 | 1 homozygous missense substitution in GUCY1A3 (c.1778G > A, p.R593H) |
| M084 | 20 | 11 | 1 | 1 homozygous splice-site substitution in NOS3 (c.1502 + 1G > C) |
| M101 | 7 | 4 | 2 | 0 |
| M116 | 11 | 11 | 4 | 0 |
Filter 1: homozygous nonsense, stop-loss, canonical splice-sites, indel and missense variants, coverage ≥ 8X, Q Phred score ≥ 30, global Minor Allele Frequency (MAF) ≤ 1%
Filter 2: MAF ≤ 1% in the ExAC ethnic subgroup fitting with the proband’s ethnicity
Filter 3: exclusion of missense variants predicted as benign by > 1/3 in-silico software (or by ≥ ½ if prediction was available for two software only)