Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000523035 | SCV000622049 | pathogenic | not provided | 2017-11-03 | criteria provided, single submitter | clinical testing | The c.318-1G>A variant in the GNPTG gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice acceptor site in intron 5. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.318-1G>A variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.318-1G>A as a pathogenic variant. |
Invitae | RCV000523035 | SCV001225802 | pathogenic | not provided | 2022-11-29 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 453175). Disruption of this splice site has been observed in individuals with mucolipidosis type III (PMID: 15060128, 29704188). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 5 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). |
Genome- |
RCV000667666 | SCV002045560 | pathogenic | GNPTG-mucolipidosis | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000667666 | SCV000792152 | likely pathogenic | GNPTG-mucolipidosis | 2017-06-09 | no assertion criteria provided | clinical testing |