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NM_000277.3(PAH):c.59A>T (p.Gln20Leu) AND Phenylketonuria

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 11, 2019
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000993617.1

Allele description [Variation Report for NM_000277.3(PAH):c.59A>T (p.Gln20Leu)]

NM_000277.3(PAH):c.59A>T (p.Gln20Leu)

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.59A>T (p.Gln20Leu)
HGVS:
  • NC_000012.12:g.102917072T>A
  • NG_008690.2:g.46339A>T
  • NM_000277.3:c.59A>TMANE SELECT
  • NM_001354304.2:c.59A>T
  • NP_000268.1:p.Gln20Leu
  • NP_001341233.1:p.Gln20Leu
  • NC_000012.11:g.103310850T>A
  • NM_000277.1:c.59A>T
  • NM_000277.2(PAH):c.59A>T
  • P00439:p.Gln20Leu
Protein change:
Q20L
Links:
UniProtKB: P00439#VAR_009239; dbSNP: rs199475662
NCBI 1000 Genomes Browser:
rs199475662
Molecular consequence:
  • NM_000277.3:c.59A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354304.2:c.59A>T - 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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001146741ClinGen PAH Variant Curation Expert Panel
reviewed by expert panel

(ClinGen PAH ACMG Specifications v1)		Uncertain significance
(Aug 11, 2019) 		germlinecuration

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Phenylketonuria and hyperphenylalaninemia in eastern Germany: a characteristic molecular profile and 15 novel mutations.

Hennermann JB, Vetter B, Wolf C, Windt E, Bührdel P, Seidel J, Mönch E, Kulozik AE.

Hum Mutat. 2000;15(3):254-60.

PubMed [citation]
PMID:
10679941

Details of each submission

From ClinGen PAH Variant Curation Expert Panel, SCV001146741.1

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

Description

VUS:The c.59A>T (p.Q20L) variant was detected in trans with a known pathogenic variant (c.1315+1G>A) in a patient with hyperphenylalaninemia (parental testing not reported) (PP4, PM3-supporting; PMID: 10679941). This variant is absent from population databases including, gnomAD, ESP, and 1000 Genomes (PM2). Computation predictors on protein structure and function indicate conflicting results (SIFT: tolerated, Polyphen: Benign, MutationTaster: Disease causing, REVEL=0.582). In summary this variant meets the criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM3-supporting, PP4.

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

Last Updated: Apr 23, 2022