NM_000317.3(PTS):c.317C>T (p.Thr106Met) AND BH4-deficient hyperphenylalaninemia A

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Oct 23, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000667396.3

Allele description [Variation Report for NM_000317.3(PTS):c.317C>T (p.Thr106Met)]

NM_000317.3(PTS):c.317C>T (p.Thr106Met)

Gene:
PTS:6-pyruvoyltetrahydropterin synthase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q23.1
Genomic location:
Preferred name:
NM_000317.3(PTS):c.317C>T (p.Thr106Met)
HGVS:
  • NC_000011.10:g.112233434C>T
  • NG_008743.1:g.12070C>T
  • NM_000317.3:c.317C>TMANE SELECT
  • NP_000308.1:p.Thr106Met
  • NC_000011.9:g.112104157C>T
  • NM_000317.2:c.317C>T
Protein change:
T106M
Links:
dbSNP: rs200712908
NCBI 1000 Genomes Browser:
rs200712908
Molecular consequence:
  • NM_000317.3:c.317C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
BH4-deficient hyperphenylalaninemia A
Synonyms:
HYPERPHENYLALANINEMIA, TETRAHYDROBIOPTERIN-DEFICIENT, DUE TO PTS DEFICIENCY; 6-pyruvoyl-tetrahydropterin synthase deficiency; Hyperphenylalanemia, BH4-deficient, A; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009863; MedGen: C0878676; Orphanet: 13; Orphanet: 238583; OMIM: 261640

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000791833Counsylcriteria provided, single submitter
Likely pathogenic
(May 24, 2017)
unknownclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV001226473Invitaecriteria provided, single submitter
Pathogenic
(Oct 23, 2020)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mutation analysis of the 6-pyruvoyl-tetrahydropterin synthase gene in Chinese hyperphenylalaninemia caused by tetrahydrobiopterin synthesis deficiency.

Liu TT, Hsiao KJ, Lu SF, Wu SJ, Wu KF, Chiang SH, Liu XQ, Chen RG, Yu WM.

Hum Mutat. 1998;11(1):76-83.

PubMed [citation]
PMID:
9450907

Phenotypic variability, neurological outcome and genetics background of 6-pyruvoyl-tetrahydropterin synthase deficiency.

Leuzzi V, Carducci CA, Carducci CL, Pozzessere S, Burlina A, Cerone R, Concolino D, Donati MA, Fiori L, Meli C, Ponzone A, Porta F, Strisciuglio P, Antonozzi I, Blau N.

Clin Genet. 2010 Mar;77(3):249-57. doi: 10.1111/j.1399-0004.2009.01306.x. Epub 2009 Jan 3.

PubMed [citation]
PMID:
20059486
See all PubMed Citations (6)

Details of each submission

From Counsyl, SCV000791833.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001226473.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces threonine with methionine at codon 106 of the PTS protein (p.Thr106Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs200712908, ExAC 0.03%). This variant has been observed in combination with another PTS variant in several individuals and families affected with hyperphenylalaninemia (PMID: 11694255, 23138986, 27246466). ClinVar contains an entry for this variant (Variation ID: 552175). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 17, 2021

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