ClinVar Miner

Submissions for variant NM_032520.5(GNPTG):c.233+1G>A

gnomAD frequency: 0.00001  dbSNP: rs376679416
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Medical Molecular Genetics Department, Human Genetics and Genome Research Division, National Research Centre RCV000667524 SCV000891128 likely pathogenic GNPTG-mucolipidosis 2018-12-10 criteria provided, single submitter clinical testing
Invitae RCV000815845 SCV000956319 pathogenic not provided 2024-01-04 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 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 (rs376679416, gnomAD 0.01%). Disruption of this splice site has been observed in individual(s) with clinical features of mucolipidosis III gamma (PMID: 30507725, 30882951). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 552294). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV000667524 SCV002045557 pathogenic GNPTG-mucolipidosis 2021-11-07 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000667524 SCV002060287 likely pathogenic GNPTG-mucolipidosis 2021-11-19 criteria provided, single submitter clinical testing NM_032520.4(GNPTG):c.233+1G>A is a canonical splice variant classified as likely pathogenic in the context of mucolipidosis III gamma. c.233+1G>A has been observed in cases with relevant disease (PMID: 30507725). Functional assessments of this variant are not available in the literature. c.233+1G>A has been observed in population frequency databases (gnomAD: AFR 0.01%). In summary, NM_032520.4(GNPTG):c.233+1G>A is a canonical splice variant in a gene where loss of function is a known mechanism of disease and is predicted to disrupt protein function. Please note: this variant was assessed in the context of healthy population screening.
GeneDx RCV000815845 SCV004034443 pathogenic not provided 2023-03-08 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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; This variant is associated with the following publications: (PMID: 30882951, 30507725, Eissa[article]2022)
Natera, Inc. RCV000667524 SCV002093785 pathogenic GNPTG-mucolipidosis 2020-09-10 no assertion criteria provided clinical testing

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