ClinVar Miner

Submissions for variant NM_000317.3(PTS):c.84-3C>G

gnomAD frequency: 0.00002  dbSNP: rs1230781262
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668809 SCV000793473 likely pathogenic 6-Pyruvoyl-tetrahydrobiopterin synthase deficiency 2017-08-22 criteria provided, single submitter clinical testing
Invitae RCV000668809 SCV000814118 pathogenic 6-Pyruvoyl-tetrahydrobiopterin synthase deficiency 2021-08-22 criteria provided, single submitter clinical testing This sequence change falls in intron 1 of the PTS gene. It does not directly change the encoded amino acid sequence of the PTS protein. It affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with biopterin deficient hyperphenylalaninemia (PMID: 9222757, 27246466). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as delK29-S32. Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects PTS function (PMID: 9222757). 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. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV001091030 SCV001246862 pathogenic not provided 2017-08-01 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001091030 SCV001446717 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
GeneDx RCV001091030 SCV001791313 pathogenic not provided 2019-03-11 criteria provided, single submitter clinical testing Published functional studies demonstrate that this variant results in complete inactivity of the PTPS enzyme (Oppliger et al., 1997) In silico analysis, which includes splice predictors and evolutionary conservation, supports a deleterious effect, and predicts abnormal gene splicing Not observed in large population cohorts (Lek et al., 2016) This variant is associated with the following publications: (PMID: 9222757, 20059486, 10585341, 27246466, 25525159)
Genome-Nilou Lab RCV000668809 SCV002014497 pathogenic 6-Pyruvoyl-tetrahydrobiopterin synthase deficiency 2021-09-05 criteria provided, single submitter clinical testing
Natera, Inc. RCV000668809 SCV002083332 pathogenic 6-Pyruvoyl-tetrahydrobiopterin synthase deficiency 2020-12-03 no assertion criteria provided clinical testing

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