ClinVar Miner

Submissions for variant NM_001042432.2(CLN3):c.461-3C>A

gnomAD frequency: 0.00003  dbSNP: rs181995380
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000732347 SCV000565798 uncertain significance not provided 2021-05-19 criteria provided, single submitter clinical testing In silico analysis supports a deleterious effect on splicing; Has not been previously published as pathogenic or benign to our knowledge; A different splice change at this residue (c.461-3C>G) has been reported in the Human Gene Mutation Database (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 9536098, 17576681)
Labcorp Genetics (formerly Invitae), Labcorp RCV000692957 SCV000820809 uncertain significance Neuronal ceroid lipofuscinosis 2022-10-17 criteria provided, single submitter clinical testing This sequence change falls in intron 7 of the CLN3 gene. It does not directly change the encoded amino acid sequence of the CLN3 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs181995380, gnomAD 0.03%). 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: 418607). 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 is not likely to affect RNA splicing. This variant disrupts the c.461-3C nucleotide in the CLN3 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 28542676; Invitae). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Eurofins Ntd Llc (ga) RCV000732347 SCV000860296 uncertain significance not provided 2018-04-03 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001785622 SCV002027123 uncertain significance Neuronal ceroid lipofuscinosis 3 2021-09-05 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000732347 SCV002541320 uncertain significance not provided 2021-08-10 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001785622 SCV002780721 uncertain significance Neuronal ceroid lipofuscinosis 3 2022-04-04 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001785622 SCV005877933 uncertain significance Neuronal ceroid lipofuscinosis 3 2024-03-25 criteria provided, single submitter clinical testing

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