NM_000317.3(PTS):c.73C>G (p.Arg25Gly) AND BH4-deficient hyperphenylalaninemia A

Clinical significance:Pathogenic (Last evaluated: Aug 21, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000545224.4

Allele description [Variation Report for NM_000317.3(PTS):c.73C>G (p.Arg25Gly)]

NM_000317.3(PTS):c.73C>G (p.Arg25Gly)

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.73C>G (p.Arg25Gly)
HGVS:
  • NC_000011.10:g.112226516C>G
  • NG_008743.1:g.5152C>G
  • NM_000317.3:c.73C>GMANE SELECT
  • NP_000308.1:p.Arg25Gly
  • NC_000011.9:g.112097239C>G
  • NM_000317.2:c.73C>G
Protein change:
R25G
Links:
dbSNP: rs1167104933
NCBI 1000 Genomes Browser:
rs1167104933
Molecular consequence:
  • NM_000317.3:c.73C>G - 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
SCV000636858Invitaecriteria provided, single submitter
Pathogenic
(Aug 21, 2020)
germlineclinical testing

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

SCV000789471Counsylno assertion criteria providedLikely pathogenic
(Feb 1, 2017)
unknownclinical testing

PubMed (2)
[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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

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
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000636858.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces arginine with glycine at codon 25 of the PTS protein (p.Arg25Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with biopterin deficient hyperphenylalanemia and to segregate with disease in a family (PMID: 23138986, 9450907). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). For these reasons, this variant has been classified as Pathogenic.

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

From Counsyl, SCV000789471.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 10, 2021

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