NM_000277.3(PAH):c.547G>T (p.Glu183Ter) AND Phenylketonuria

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 7, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001223829.6

Allele description [Variation Report for NM_000277.3(PAH):c.547G>T (p.Glu183Ter)]

NM_000277.3(PAH):c.547G>T (p.Glu183Ter)

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.547G>T (p.Glu183Ter)

HGVS:

NC_000012.12:g.102855295C>A
NG_008690.2:g.108116G>T
NM_000277.3:c.547G>TMANE SELECT
NM_001354304.2:c.547G>T
NP_000268.1:p.Glu183Ter
NP_001341233.1:p.Glu183Ter
NC_000012.11:g.103249073C>A
NM_000277.1:c.547G>T

Protein change:

E183*

Links:

dbSNP: rs199475664

NCBI 1000 Genomes Browser:

rs199475664

Molecular consequence:

NM_000277.3:c.547G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001354304.2:c.547G>T - nonsense - [Sequence Ontology: SO:0001587]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001395995	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 7, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 1301187, 9634518, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001395995

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 7, 2019)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular basis of phenylketonuria and related hyperphenylalaninemias: mutations and polymorphisms in the human phenylalanine hydroxylase gene.

Eisensmith RC, Woo SL.

Hum Mutat. 1992;1(1):13-23. Review.

PubMed [citation]

PMID:: 1301187

A European multicenter study of phenylalanine hydroxylase deficiency: classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype.

Guldberg P, Rey F, Zschocke J, Romano V, François B, Michiels L, Ullrich K, Hoffmann GF, Burgard P, Schmidt H, Meli C, Riva E, Dianzani I, Ponzone A, Rey J, Güttler F.

Am J Hum Genet. 1998 Jul;63(1):71-9. Erratum in: Am J Hum Genet 1998 Oct;63(4):1252-3.

PubMed [citation]

PMID:: 9634518
PMCID:: PMC1377241

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001395995.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in PAH are known to be pathogenic (PMID: 1301187, 9634518). This variant has not been reported in the literature in individuals with PAH-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu183*) in the PAH gene. It is expected to result in an absent or disrupted protein product.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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