Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Brain and Mitochondrial Research, |
RCV002267780 | SCV002062065 | pathogenic | Infantile liver failure syndrome 2 | criteria provided, single submitter | research | The NM_015909.3(NBAS):c.1213C>T; p.(Arg405*) variant has been identified in one individual with NBAS-associated RALF (MIM#616483). The variant was absent from a large population database (gnomAD v2.1.1 (accessed 07/10/2020)). It has not been previously reported in association with clinical disease, however many upstream and downstream variants also resulting in a premature termination codon have been reported (PMID: 31761904). cDNA studies confirmed the transcript to be subject to degradation by nonsense mediated decay (NMD). Western blotting of fibroblast cell lysates showed decreased NBAS protein expression. The phenotype was a strong and specific match for NBAS-associated RALF (MIM#616483). cDNA studies confirmed compound heterozygosity with a pathogenic variant. Based on current information this variant has been classified as PATHOGENIC. | |
| Labcorp Genetics |
RCV001869650 | SCV002213657 | pathogenic | not provided | 2023-04-01 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg405*) in the NBAS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NBAS are known to be pathogenic (PMID: 26073778, 26541327, 27789416, 28031453). This variant is present in population databases (rs376113678, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with NBAS-related conditions. ClinVar contains an entry for this variant (Variation ID: 1335898). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002222731 | SCV002500659 | pathogenic | Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins | 2024-04-30 | criteria provided, single submitter | clinical testing | Variant summary: NBAS c.1213C>T (p.Arg405X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 8e-06 in 251276 control chromosomes. c.1213C>T has been reported in the literature in individuals affected with Liver Failure Acute Infantile, Type 2 (example: Akesson_2022). These data indicate that the variant is likely associated with disease. The following publication has been ascertained in the context of this evaluation (PMID: 35433172). ClinVar contains an entry for this variant (Variation ID: 1335898). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Institute of Human Genetics, |
RCV004815643 | SCV005068960 | pathogenic | Retinal dystrophy | 2022-01-01 | criteria provided, single submitter | clinical testing |