ClinVar Miner

Submissions for variant NM_001042432.2(CLN3):c.47-1G>A

gnomAD frequency: 0.00001  dbSNP: rs1555469477
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000670278 SCV000795112 likely pathogenic Neuronal ceroid lipofuscinosis 3 2017-10-27 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000778462 SCV000914714 uncertain significance Neuronal ceroid lipofuscinosis 2018-11-07 criteria provided, single submitter clinical testing The CLN3 c.47-1G>A variant occurs in a canonical splice site (acceptor) and is therefore predicted to disrupt or distort the normal gene product. A literature search was performed for the gene and cDNA change. No publications were found based on this search. This variant is not found in the 1000 Genomes Project, Exome Sequencing Project, Exome Aggregation Consortium, or Genome Aggregation Database in a region of good sequencing coverage. It is therefore presumed to be rare. Based on the potential impact of splice acceptor variants and the lack of clarifying evidence, the c.47-1G>A variant is classified as a variant of unknown significance but suspicious for pathogenicity for neuronal ceroid-lipofuscinosis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000778462 SCV001404997 likely pathogenic Neuronal ceroid lipofuscinosis 2023-11-28 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 2 of the CLN3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CLN3 are known to be pathogenic (PMID: 9311735, 28542676). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CLN3-related conditions. ClinVar contains an entry for this variant (Variation ID: 554608). 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.
Baylor Genetics RCV000670278 SCV004214321 likely pathogenic Neuronal ceroid lipofuscinosis 3 2024-01-05 criteria provided, single submitter clinical testing

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