Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Medical Molecular Genetics Department, |
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- |
RCV000667524 | SCV002045557 | pathogenic | GNPTG-mucolipidosis | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
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. |
Gene |
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, |
RCV000667524 | SCV002093785 | pathogenic | GNPTG-mucolipidosis | 2020-09-10 | no assertion criteria provided | clinical testing |