Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001852908 | SCV002172301 | likely pathogenic | not provided | 2023-08-10 | criteria provided, single submitter | clinical testing | Disruption of this splice site has been observed in individual(s) with mitochondrial complex I deficiency (PMID: 29417091, 31917109, 32518176). This variant is present in population databases (rs751631278, gnomAD 0.003%). This sequence change affects a donor splice site in intron 8 of the NUBPL gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NUBPL are known to be pathogenic (PMID: 23553477, 31917109). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 50216). |
| OMIM | RCV000043478 | SCV000067288 | pathogenic | Mitochondrial complex 1 deficiency, nuclear type 21 | 2013-04-23 | no assertion criteria provided | literature only |