Description
The p.Lys271Asn variant in UBA5 has not been previously reported in individuals with disease or in large population studies. The variant was detected in trans w ith a pathogenic hypomorphic variant (p.Ala371Thr) in this patient with infantil e spasms, intractable epilepsy, microcephaly, cortical vision impairment, and gl obal developmental delays with regression. Computational prediction tools and am ino acid conservation analysis suggest that the p.Lys271Asn variant may impact t he protein, though this information is not predictive enough to determine pathog enicity through a protein sequence change. This variant is located in the first base of the exon, which is part of the 3? splice region, making a splicing impac t possible; however, this position is not highly conserved such that a predicted impact to splicing is unclear. In summary, the clinical significance of the p.L ys271Asn variant is uncertain by ACMG/AMP criteria. ACMG/AMP Criteria applied: P M3, PM2, PP3.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | not provided | not provided | not provided | not provided | | 2 | not provided | 1 | not provided |
