Table 1. Effect predictions for ZNF423 substitution variants modeled in this study.
Variant (domain) shows position relative to NP_ 055884.2, single-letter amino acid codes, and position relative to C2H2 zinc fingers (ZF). Column hg38 shows nucleotide position in the hg38 reference assembly with reference/variant nucleotide. For the gnomAD database (v2), allele count and minor allele frequency (MAF) are given. ClinVar assertions were current at time of writing. Categorical calls and scores are shown for 8 variant effect predictors.
| Variant (domain) | hg38 | gnomAD (MAF) | ClinVar 2019 | PolyPhen2 (HVAR) | SIFT (Score) | PROVEAN | Mutation Taster (rankscore) | Mutation Assessor (rankscore) | VEST3 Rank score | CADD PHRED | Envision |
|---|---|---|---|---|---|---|---|---|---|---|---|
| R89H (ZF1) | 16:49730782 C/T | 18 (6.4 e-5) | Likely pathogenic | Benign (0.001) | Tolerated (0.282) | Neutral (0.19) | Polymorphism (0.261) | Neutral (0.016) | 0.126 | 19.16 | 0.99 |
| G132V (ZF1-2 linker) | 16:49638757 C/A | 0 | - | Damaging (1) | Damaging (0.002) | Deleterious (-2.67) | Disease causing (0.81) | Low (0.225) | 0.883 | 25.6 | 0.85 |
| S382P (ZF8-9 linker) | 16:49638008 A/G | 215 (7.6 e-4) | Uncertain significance | Possibly damaging (0.72) | Tolerated (0.254) | Neutral (-1.65) | Disease causing (0.345) | Low (0.498) | 0.682 | 24.4 | 0.92 |
| R760C (ZF18) | 16:49636874 G/A | 11 (3.8 e-5) | - | Probably damaging (0.82) | Damaging (0.001) | Deleterious (-4.83) | Disease causing (0.588) | Low (0.304) | 0.904 | 28.9 | 0.74 |
| P913L (ZF21) | 16:49636414 G/A | 47 (1.7e-4) | Pathogenic | Probably damaging (0.92) | Damaging (0.010) | Deleterious (-3.87) | Disease causing (0.81) | Medium (0.833) | 0.842 | 28.5 | 0.89 |
| Q1008H (ZF24) | 16:49636128 C/G | 7 (2.8e-5) | - | Probably damaging (0.88) | Damaging (0.000) | Deleterious (-3.61) | Disease causing (0.457) | Medium (0.53) | 0.848 | 25.3 | 0.93 |
| Y1064C (C4) | 16:49635961 T/C | 1 (4.2e-6) | - | Probably damaging (0.75) | Damaging (0.031) | Deleterious (-5.02) | Disease causing (0.548) | Low (0.246) | 0.815 | 28.1 | 0.74 |
| K1071Q (C4) | 16:49635941 T/G | 0 | - | Probably damaging (0.65) | Damaging (0.036) | Neutral (-1.52) | Disease causing (0.465) | Low (0.246) | 0.577 | 28.5 | 0.92 |
| E1124K (ZF26) | 16:49635782 C/T | 8 (3.2e-5) | Likely pathogenic | Possibly damaging (0.54) | Tolerated (0.092) | Neutral (-1.64) | Disease causing (0.548) | Medium (0.562) | 0.883 | 23.6 | 0.98 |
| H1277Y (ZF30) | 16:49491301 G/A | 0 | Pathogenic | Benign (0.04) | Damaging (0.002) | Deleterious (-3.93) | Disease causing (0.53) | Medium (0.924) | 0.951 | 24.5 | 0.92 |