Table 5.
Semi-quantitative approach for TP53 variant bioinformatic prediction using Align-GVGD class (optimized pMSA) and BayesDel score
| Category | Assumed pathogenic (n) | % | Assumed benign (n) | % | Positive LR (95% CI) | Proposed ACMG/AMP rule |
|---|---|---|---|---|---|---|
| Optimized Align-GVGD C65 + BayesDel ≥0.16 | 146 | 59.11 | 0 | NA | 59.11 | Moderate evidence of pathogenicity (new rule) |
| Optimized Align-GVGD C65 + BayesDel <0.16 | 0 | NA | 0 | NA | NA | No data |
| Optimized Align-GVGD C55-C25 + BayesDel ≥0.16 | 50 | 20.24 | 3 | 4.22 | 4.79 (1.54, 14.90) | Supporting evidence of pathogenicity (PP3) |
| Optimized Align-GVGD C55-C25 + BayesDel <0.16 | 7 | 2.83 | 5 | 8.45 | 0.33 (0.12, 0.97) | No evidence |
| Optimized Align-GVGD C15 + BayesDel ≥0.16 | 13 | 5.26 | 3 | 4.22 | 1.25 (0.37, 4.25) | No evidence |
| Optimized Align-GVGD C15 + BayesDel <0.16 | 4 | 1.62 | 5 | 7.04 | 0.23 (0.06, 0.83) | Supporting evidence of benign impact (BP4) |
| Optimized Align-GVGD C0 + BayesDel ≥0.16 | 10 | 4.05 | 5 | 7.04 | 0.57 (0.20, 1.63) | No evidence |
| Optimized Align-GVGD C0 + BayesDel <0.16 | 18 | 7.29 | 49 | 69.01 | 0.11 (0.07, 0.17) | Supporting evidence of benign impact (BP4) |
| Total | 247 | 71 |