Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000489617 | SCV000576902 | likely pathogenic | not provided | 2017-04-15 | criteria provided, single submitter | clinical testing | The Y187X nonsense variant in the C8orf38 gene is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Y187X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Although this variant has not been reported previously to our knowledge, loss of function is reported to be the mechanism of disease for the C8orf38 gene; in summary, we interpret Y187X to be a likely pathogenic variant (McKenzie et al., 2011). |
Ambry Genetics | RCV003168994 | SCV003888353 | pathogenic | Inborn genetic diseases | 2023-02-08 | criteria provided, single submitter | clinical testing | The c.561C>G (p.Y187*) alteration, located in exon 5 (coding exon 5) of the NDUFAF6 gene, consists of a C to G substitution at nucleotide position 561. This changes the amino acid from a tyrosine (Y) to a stop codon at amino acid position 187. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the available evidence, this alteration is classified as pathogenic. |
Labcorp Genetics |
RCV000489617 | SCV004392386 | pathogenic | not provided | 2023-07-14 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 426455). This variant has not been reported in the literature in individuals affected with NDUFAF6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr187*) in the NDUFAF6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NDUFAF6 are known to be pathogenic (PMID: 28639102, 30642748). For these reasons, this variant has been classified as Pathogenic. |