ClinVar Miner

Submissions for variant NM_032520.5(GNPTG):c.742-1G>T

gnomAD frequency: 0.00003  dbSNP: rs373976323
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668332 SCV000792911 likely pathogenic GNPTG-mucolipidosis 2017-08-03 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000668332 SCV000914706 uncertain significance GNPTG-mucolipidosis 2018-11-20 criteria provided, single submitter clinical testing This variant occurs in a canonical splice site (acceptor) and is therefore predicted to disrupt or distort the normal gene product. It was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018) and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene and cDNA change. No publications were found based on this search. Due to the potential impact of splice acceptor variants and the lack of clarifying evidence, this variant is classified as a variant of uncertain significance but suspicious for pathogenicity for this disease.
Genome-Nilou Lab RCV000668332 SCV002045553 likely pathogenic GNPTG-mucolipidosis 2021-11-07 criteria provided, single submitter clinical testing
Invitae RCV001855495 SCV002305530 likely pathogenic not provided 2024-01-29 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 9 of the GNPTG 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 GNPTG are known to be pathogenic (PMID: 19370764, 20301784). This variant is present in population databases (rs373976323, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with GNPTG-related conditions. ClinVar contains an entry for this variant (Variation ID: 552977). 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.
GeneDx RCV001855495 SCV003798960 uncertain significance not provided 2022-08-04 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge

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