Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001379168 | SCV001576918 | pathogenic | not provided | 2023-09-26 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 11 of the CNGB3 gene. It does not directly change the encoded amino acid sequence of the CNGB3 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has been observed in individual(s) with achromatopsia (PMID: 27479814, 28795510; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 427703). 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. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000498797 | SCV004029596 | likely pathogenic | Achromatopsia 3 | 2023-07-27 | criteria provided, single submitter | clinical testing | Variant summary: CNGB3 c.1320+4A>G alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 3/4 computational tools predict no significant impact on normal splicing, while 1 tool predicts that it weakens the canonical 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 250378 control chromosomes (gnomAD). c.1320+4A>G has been reported in the literature in individuals affected with Achromatopsia (Langlo_2016, Mayer_2017, Ganapathi_2022), and some were reported as compound heterozygous with other (likely) pathogenic variants. These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 27479814, 28795510, 35672425). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as pathogenic, and one classified it as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Molecular Genetics Laboratory, |
RCV000498797 | SCV000575849 | uncertain significance | Achromatopsia 3 | 2017-03-27 | no assertion criteria provided | research |