ClinVar Miner

Submissions for variant NM_019098.4(CNGB3):c.467C>T (p.Ser156Phe) (rs139207764)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000498220 SCV000795326 uncertain significance Achromatopsia 3 2017-11-03 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000498220 SCV000916239 likely pathogenic Achromatopsia 3 2018-12-14 criteria provided, single submitter clinical testing The CNGB3 c.467C>T (p.Ser156Phe) missense variant has been reported in three studies and identified in at least four unrelated compound heterozygotes, all affected with achromatopsia (Kohl et al. 2005; Zein et al. 2014; Zelinger et al. 2015). The variant was absent from 100 healthy controls but is reported at a frequency of 0.000394 in the Ashkenazi Jewish population in the Genome Aggregation Database. Meighan et al. (2015) performed functional studies using Xenopus oocytes and the p.Ser156Phe variant was found not to interfere with the formation of functional A3+B3 channels or to cause significant changes to CNG channel behavior compared to wild type. The variant is not found in a highly conserved region of the protein (Meighan et al. 2015). Based on the evidence, the p.Ser156Phe variant is classified as likely pathogenic for achromatopsia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000815424 SCV000955875 likely pathogenic not provided 2018-12-03 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 156 of the CNGB3 protein (p.Ser156Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is present in population databases (rs139207764, ExAC 0.01%). This variant has been observed in individuals with achromatopsia (PMID: 25616768, 15657609, 28795510). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 427671). This variant has been reported to have insufficient data to determine the effect on CNGB3 protein function (PMID: 26106334). 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.
Illumina Clinical Services Laboratory,Illumina RCV001159644 SCV001321369 uncertain significance Stargardt disease 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Molecular Genetics Laboratory,Institute for Ophthalmic Research RCV000498220 SCV000575805 likely pathogenic Achromatopsia 3 2017-03-27 no assertion criteria provided research
Sharon lab,Hadassah-Hebrew University Medical Center RCV001002981 SCV001161034 likely pathogenic Achromatopsia 2019-06-23 no assertion criteria provided research
Natera, Inc. RCV001002981 SCV001454558 likely pathogenic Achromatopsia 2020-09-16 no assertion criteria provided clinical testing

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