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

gnomAD frequency: 0.00002  dbSNP: rs1230781262

Total submissions: 10

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
Labcorp Genetics (formerly Invitae), Labcorp	RCV000668809	SCV000814118	pathogenic	6-Pyruvoyl-tetrahydrobiopterin synthase deficiency	2024-01-27	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. This variant is not present in population databases (gnomAD 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 being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as delK29-S32. ClinVar contains an entry for this variant (Variation ID: 553378). 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
Baylor Genetics	RCV000668809	SCV004207151	pathogenic	6-Pyruvoyl-tetrahydrobiopterin synthase deficiency	2024-01-20	criteria provided, single submitter	clinical testing
Laboratory of Medical Genetics, National & Kapodistrian University of Athens	RCV000668809	SCV005051948	pathogenic	6-Pyruvoyl-tetrahydrobiopterin synthase deficiency	2024-02-01	criteria provided, single submitter	curation
Fulgent Genetics, Fulgent Genetics	RCV000668809	SCV005681034	pathogenic	6-Pyruvoyl-tetrahydrobiopterin synthase deficiency	2024-03-16	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