NM_000277.3(PAH):c.158G>A (p.Arg53His) AND Phenylketonuria

Clinical significance:Uncertain significance (Last evaluated: Aug 10, 2018)

Review status:3 stars out of maximum of 4 stars

reviewed by expert panel

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000490373.7

Allele description [Variation Report for NM_000277.3(PAH):c.158G>A (p.Arg53His)]

NM_000277.3(PAH):c.158G>A (p.Arg53His)

Gene:
PAH:phenylalanine hydroxylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q23.2
Genomic location:
Preferred name:
NM_000277.3(PAH):c.158G>A (p.Arg53His)
Other names:
NM_000277.2(PAH):c.158G>A
HGVS:
  • NC_000012.12:g.102912801C>T
  • NG_008690.2:g.50610G>A
  • NM_000277.3:c.158G>A
  • NM_001354304.2:c.158G>A
  • NP_000268.1:p.Arg53His
  • NP_001341233.1:p.Arg53His
  • NC_000012.11:g.103306579C>T
  • NM_000277.1:c.158G>A
  • NM_000277.2:c.158G>A
  • P00439:p.Arg53His
Protein change:
R53H
Links:
UniProtKB: P00439#VAR_000878; dbSNP: rs118092776
NCBI 1000 Genomes Browser:
rs118092776
Molecular consequence:
  • NM_000277.3:c.158G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354304.2:c.158G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Phenylketonuria (PKU)
Synonyms:
Phenylketonurias; Classic phenylketonuria
Identifiers:
MedGen: C0751434; Orphanet: 716; OMIM: 261600

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000267433Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Centercriteria provided, single submitter
Uncertain significance
(Mar 18, 2016)
germlinereference population

PubMed (2)
[See all records that cite these PMIDs]

SCV000852170ClinGen PAH Variant Curation Expert Panelreviewed by expert panel
Uncertain significance
(Aug 10, 2018)
germlinecuration

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV000853180SingHealth Duke-NUS Institute of Precision Medicineno assertion criteria providedLikely benign
(Jun 7, 2017)
germlinecuration

SCV001138806Mendelicscriteria provided, single submitter
Uncertain significance
(May 28, 2019)
unknownclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedcuration
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
East Asiangermlineunknown3not providednot providednot providednot providedreference population

Citations

PubMed

Identification of three novel mutations in Korean phenylketonuria patients: R53H, N207D, and Y325X.

Park YS, Seoung CS, Lee SW, Oh KH, Lee DH, Yim J.

Hum Mutat. 1998;Suppl 1:S121-2. No abstract available.

PubMed [citation]
PMID:
9452061

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753
See all PubMed Citations (3)

Details of each submission

From Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center, SCV000267433.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1East Asian3not providednot providedreference population PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided3not providednot providednot provided

From ClinGen PAH Variant Curation Expert Panel, SCV000852170.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)

Description

PAH-specific ACMG/AMP criteria applied: BS1: MAF=0.01596 in ExAC (138/8648) and 0.0104 in gnomAD (265/18868 with 3 homozygotes); PP4: Detected in a patient with mild hyperphe (PMID:24401910); PM3: Detected with V388L (LP) (PMID:24401910). In summary this variant meets criteria to be classified as uncertain significance for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (BS1, PP4, PM3).

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

From SingHealth Duke-NUS Institute of Precision Medicine, SCV000853180.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

From Mendelics, SCV001138806.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 10, 2020

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