Table 3.
Variants identified
| Variant/family no. | Variant | Predictive tools | Conservation | gnomAD AF | ||
|---|---|---|---|---|---|---|
| 1 |
c957+1G>T homozygous GRCh37:g.14504577C>A |
Human Splicing Finder Donor site loss (− 26.84) Splice Site Prediction by Neural Network Donor site loss (Mutant score = 0) MaxEntScan Donor site loss (− 78.36) SpliceAI Donor site loss New donor site created causing a 1 nucleotide frameshift |
Absent | |||
| 2 |
c.1651T>G (p.Phe551Val) homozygous GRCh37:g.14496127A>C |
Polyphen-2 | Probably damaging | Nucleotide conservation | PhyloP 5.21 (strongly conserved) | Absent |
| SIFT | Deleterious | Amino acid conservation |
High, to Baker’s Yeast ConSurf 8/9 |
|||
| CADD (Phred) | 32 | |||||
The variant identified in Family 1 affects the +1 donor position of exon 8. Note the results from SpliceAI which predicts both donor site loss and creation of a new donor site (verified by experimental data in Fig. 2). The missense variant in Family 2 is predicted to be deleterious by a number of tools