ClinVar Miner

Submissions for variant NM_000310.4(PPT1):c.362+5G>A

dbSNP: rs796052924
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188713 SCV000242337 pathogenic not provided 2013-07-19 criteria provided, single submitter clinical testing c.362+5 G>A: IVS3+5 G>A in intron 3 of the PPT1 gene (NM_000310.3). The c.362+5 G>A is predicted to destroy the consensus splice donor site in intron 3, leading to abnormal gene splicing. Although this mutation has not been previously reported to our knowledge, other mutations affecting this splice donor site have been reported in association with neuronal ceroid lipofuscinosis (NCL). Therefore, c.362+5 G>A is considered a disease-causing mutation. The variant is found in EPILEPSY panel(s).
Invitae RCV001090090 SCV003450384 uncertain significance Neuronal ceroid lipofuscinosis 1 2022-03-29 criteria provided, single submitter clinical testing This sequence change falls in intron 3 of the PPT1 gene. It does not directly change the encoded amino acid sequence of the PPT1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with neurodevelopmental conditions, leukodystrophy, and epilepsy and/or PPT-related conditions (PMID: 29655203, 33547378; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 206643). 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 may disrupt the consensus splice site. 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.
3billion RCV001090090 SCV004013803 uncertain significance Neuronal ceroid lipofuscinosis 1 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Intron variant. In silico tools predict the variant to alter splicing and produce an abnormal transcript (SpliceAI: 0.91). The variant has been reported to be associated with PPT1 related disorder (ClinVar ID: VCV000206643 / PMID: 29655203). However, the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as Uncertain significance according to the recommendation of ACMG/AMP guideline.
Baylor Genetics RCV001090090 SCV004204150 likely pathogenic Neuronal ceroid lipofuscinosis 1 2023-07-06 criteria provided, single submitter clinical testing
Myelin Disorders Clinic-Children's Medical Center/Medical Genetics Lab-Tarbiat Modares University, Children's Medical Center, Pediatrics Center of Excellence, RCV001090090 SCV001244931 uncertain significance Neuronal ceroid lipofuscinosis 1 no assertion criteria provided clinical testing

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