ClinVar Miner

Submissions for variant NM_001008212.2(OPTN):c.1533-3C>T

gnomAD frequency: 0.00003  dbSNP: rs373981784
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001057571 SCV001222070 uncertain significance Primary open angle glaucoma; Amyotrophic lateral sclerosis type 12; Glaucoma 1, open angle, E 2023-09-10 criteria provided, single submitter clinical testing 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. This sequence change falls in intron 12 of the OPTN gene. It does not directly change the encoded amino acid sequence of the OPTN protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs373981784, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with OPTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 852864). 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.
GeneDx RCV001760007 SCV001990198 uncertain significance not provided 2019-07-18 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
Dept. of Medical Genetics, Telemark Hospital Trust, Telemark Hospital Trust RCV001843559 SCV002103166 uncertain significance Amyotrophic lateral sclerosis 2022-01-01 criteria provided, single submitter research
Ambry Genetics RCV002400329 SCV002706672 uncertain significance Inborn genetic diseases 2021-12-06 criteria provided, single submitter clinical testing The c.1533-3C>T intronic variant results from a C to T substitution 3 nucleotides upstream from coding exon 12 in the OPTN gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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