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:
8 submissions [Details]
Record status:
current
Accession:
RCV000490373.12

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>AMANE SELECT
  • 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; Oligophrenia phenylpyruvica; Folling disease
Identifiers:
MONDO: MONDO:0009861; MedGen: C0031485; 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]

SCV000754088Invitaecriteria provided, single submitter
Benign
(Dec 4, 2020)
germlineclinical testing

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

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,

SCV001266460Illumina Laboratory Services,Illuminacriteria provided, single submitter
Likely benign
(Apr 27, 2017)
germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Citation Link,

SCV001455418Natera, Inc.no assertion criteria providedBenign
(Jan 6, 2020)
germlineclinical testing

SCV001716364Nilou-Genome Labcriteria provided, single submitter
Uncertain significance
(May 18, 2021)
germlineclinical testing

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

Summary from all submissions

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

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

The mutation spectrum of the phenylalanine hydroxylase (PAH) gene and associated haplotypes reveal ethnic heterogeneity in the Taiwanese population.

Liang Y, Huang MZ, Cheng CY, Chao HK, Fwu VT, Chiang SH, Hsiao KJ, Niu DM, Su TS.

J Hum Genet. 2014 Mar;59(3):145-52. doi: 10.1038/jhg.2013.136. Epub 2014 Jan 9.

PubMed [citation]
PMID:
24401910
See all PubMed Citations (10)

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 Invitae, SCV000754088.4

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

From Illumina Laboratory Services,Illumina, SCV001266460.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

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

From Natera, Inc., SCV001455418.1

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

From Nilou-Genome Lab, SCV001716364.1

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

Last Updated: Jan 8, 2022

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