Table 2.
Prediction analysis and ACMG classification of the seven SMCHD1 (NM_015295.2) mutations. ESS: exonic silencer site; ESE: exonic splicing enhancer; WT: wild-type
| SMCHD1 mutations | MutationTaster | SMART | Human splicing finder | ACMG |
|---|---|---|---|---|
| c.182_183dupGT | Disease-causing | Loss of GHKL-ATPase domain and SMC hinge domain | Disruption of a donor splice site; activation of an exonic cryptic donor site or creation of an ESS | Likely pathogenic |
| c.2129dupC | Disease-causing | Loss of SMC hinge domain | No significant splicing motif alteration detected | Pathogenic |
| c.3469G>T | Disease-causing | Loss of SMC hinge domain | Alteration of an ESE | Pathogenic |
| c.5150_5151delAA | Disease-causing | Loss of SMC hinge domain | Creation of an ESS or alteration of an ESE | Pathogenic |
| c.1131+2_1131+5delTAAG | Disease-causing | NA | Alteration of the WT donor site | Likely pathogenic |
| c.853G>C | Disease-causing | No significant alteration of domain organization | No significant splicing motif alteration detected | Likely pathogenic |
| c.3010A>T | Disease-causing | Loss of SMC hinge domain | Creation of an ESS or alteration of an ESE | Pathogenic |