Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000668475 | SCV000793085 | uncertain significance | 3-Methylglutaconic aciduria type 3 | 2017-08-02 | criteria provided, single submitter | clinical testing | |
Kasturba Medical College, |
RCV000668475 | SCV001548568 | uncertain significance | 3-Methylglutaconic aciduria type 3 | 2020-11-12 | criteria provided, single submitter | clinical testing | |
Suma Genomics | RCV000668475 | SCV002097002 | uncertain significance | 3-Methylglutaconic aciduria type 3 | criteria provided, single submitter | clinical testing | ||
Labcorp Genetics |
RCV001855499 | SCV002295211 | likely pathogenic | 3-Methylglutaconic aciduria type 3; Optic atrophy 3 | 2023-07-13 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 1 of the OPA3 gene. It does not directly change the encoded amino acid sequence of the OPA3 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has been observed in individual(s) with OPA3-related 3-methylglutaconic aciduria (PMID: 24749080). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 553096). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
Neuberg Centre For Genomic Medicine, |
RCV000668475 | SCV004047221 | uncertain significance | 3-Methylglutaconic aciduria type 3 | criteria provided, single submitter | clinical testing | The OPA3 c.142+5G>C variant has been reported in compond heterozygous state in individuals affected with 3-methylglutaconic aciduria, type III (Christina et. al., 2014). The c.142+5G>C variant is novel (not in any individuals) in 1000 Genomes and has allele frequency of 0.0004% in gnomAD database. This variant has been reported to the ClinVar database as Likely pathogenic and Uncertain Significance. The variant does not affect an invariant splice nucleotide and in the absence of functional studies, this variant has been classified as Variant of Uncertain Significance (VUS). |