Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000489731 | SCV000577709 | likely pathogenic | not provided | 2021-12-07 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 26073778, 26578240, 26541327) |
| Labcorp Genetics |
RCV000489731 | SCV002128879 | uncertain significance | not provided | 2022-02-03 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 842 of the NBAS protein (p.Val842Phe). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with recurrent acute liver failure (PMID: 26073778). ClinVar contains an entry for this variant (Variation ID: 427078). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Undiagnosed Diseases Network, |
RCV002280120 | SCV002568419 | uncertain significance | Infantile liver failure syndrome 2 | 2022-06-13 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005056068 | SCV005725684 | uncertain significance | not specified | 2024-11-26 | criteria provided, single submitter | clinical testing | Variant summary: NBAS c.2524G>T (p.Val842Phe) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251372 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2524G>T has been reported in the literature in at-least one individual affected with Liver Failure Acute Infantile (example, Haack_2015). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 26073778). ClinVar contains an entry for this variant (Variation ID: 427078). Based on the evidence outlined above, the variant was classified as uncertain significance. |