Table 2.
Annotation of the two UBA5 mutations detected in the sisters
| mutation A (maternal) | mutation B (paternal) | |
|---|---|---|
| Position (GRCh38) | chr3:132,675,903 | chr3:132,671,881 |
| Variant consequence | Missense | Splice region (donor site) leading to a LoF |
| Variant genotype | Heterozygous | Heterozygous |
| cDNA changea | c.1111G > A (NM_024818.3) | c.684G > A (NM_024818.3) |
| Protein changea | p.Ala371Thr (NP_079094.1) | p.(Ala228=) (NP_079094.1) |
| Transcript length | 404 AA (NM_024818.3) | 404 AA (NM_024818.3) |
| Exon/exons in transcript | 11/12 (NM_024818.3) | 7/12 (NM_024818.3) |
| Allelic frequency Iceland | 0.38% (249/30,067 Icelanders) | Absent from 30,064 Icelanders |
| Allelic frequency abroad (gnomAD [7]) | 0.58% (75/12,985 Finnish individuals) 0.25% (157/62,175 European, non-Finnish individuals)b |
Seen in one individual (European, non-Finnish) out of 138,632 |
| SIFTc | Deleterious | NA |
| PolyPhen-2c | Possibly damaging | NA |
| GERP conservation scored | Highly conserved (5.44) | Highly conserved (4.95) |
| Disease in literature | Early Infantile Epileptic Encephalopathy-44 [2–4] | |
aFunctional annotation as suggested by the Human Genome Variation Society (HGVS)
bA lower frequency in other populations
cSIFT and PolyPhen-2 are scores for the predicted effect of amino acid substitution on protein structure and function
dThe Genomic Evolutionary Rate Profiling (GERP) framework gives a measure of evolutionary conservation based on the alignment of sequences from 29 mammalian species