NM_000277.3(PAH):c.800A>T (p.Gln267Leu) 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:
2 submissions [Details]
Record status:
current
Accession:
RCV000210763.1

Allele description [Variation Report for NM_000277.3(PAH):c.800A>T (p.Gln267Leu)]

NM_000277.3(PAH):c.800A>T (p.Gln267Leu)

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.800A>T (p.Gln267Leu)
Other names:
NM_000277.2(PAH):c.800A>T
HGVS:
  • NC_000012.12:g.102852857T>A
  • NG_008690.2:g.110554A>T
  • NM_000277.3:c.800A>TMANE SELECT
  • NM_001354304.2:c.800A>T
  • NP_000268.1:p.Gln267Leu
  • NP_001341233.1:p.Gln267Leu
  • NC_000012.11:g.103246635T>A
  • NM_000277.1:c.800A>T
Protein change:
Q267L
Links:
dbSNP: rs778154939
NCBI 1000 Genomes Browser:
rs778154939
Molecular consequence:
  • NM_000277.3:c.800A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354304.2:c.800A>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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
SCV000266852Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospitalno assertion criteria providedLikely pathogenic
(Oct 1, 2013)
paternalclinical testing

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

Citation Link,

SCV000852111ClinGen PAH Variant Curation Expert Panelreviewed by expert panel
Uncertain significance
(Aug 10, 2018)
germlinecuration

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

Citation Link

Description

This variant was reported to be a novel likely pathogenic mutation for the first time by us.

SCV000266852

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration
Chinesepaternalyes11not provided70not providedclinical testing

Citations

PubMed

Molecular characterization of phenylketonuria and tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency in Japan.

Okano Y, Kudo S, Nishi Y, Sakaguchi T, Aso K.

J Hum Genet. 2011 Apr;56(4):306-12. doi: 10.1038/jhg.2011.10. Epub 2011 Feb 10.

PubMed [citation]
PMID:
21307867

Molecular characterisation of phenylketonuria in a Chinese mainland population using next-generation sequencing.

Li N, Jia H, Liu Z, Tao J, Chen S, Li X, Deng Y, Jin X, Song J, Zhang L, Liang Y, Wang W, Zhu J.

Sci Rep. 2015 Oct 27;5:15769. doi: 10.1038/srep15769.

PubMed [citation]
PMID:
26503515
PMCID:
PMC4621502
See all PubMed Citations (3)

Details of each submission

From Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, SCV000266852.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Chinese1not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1paternalyes70not providednot provided1not provided1not provided

From ClinGen PAH Variant Curation Expert Panel, SCV000852111.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (3)

Description

PAH-specific ACMG/AMP criteria applied: PM2: Absent from 1000G, ESP. Extremely low frequency in ExAC and gnomAD ( 0.00001, 0.000004063); PP3: Predicted deleterious in SIFT, Polyphen2, MutationTaster. REVEL=0.975; PP4_Moderate: Q267L found in 1 Japanese PKU allele and in 1 Chinese PKU patient. Analysis of dihydropteridine reductase activity in red blood cells, biopterin loading test and/or pteridine analysis in urine was performed in the Japanese study. Upgraded per ClinGen Metabolic workgroup. (PMID:21307867; PMID:24078561; PMID:26503515). 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: (PM2, PP3, PP4_Moderate).

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

Last Updated: Aug 7, 2021

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