NM_000277.3(PAH):c.428A>G (p.Asp143Gly) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 2, 2023
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:: RCV000088914.3

Allele description [Variation Report for NM_000277.3(PAH):c.428A>G (p.Asp143Gly)]

NM_000277.3(PAH):c.428A>G (p.Asp143Gly)

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.428A>G (p.Asp143Gly)

HGVS:

NC_000012.12:g.102877475T>C
NG_008690.2:g.85936A>G
NM_000277.3:c.428A>GMANE SELECT
NM_001354304.2:c.428A>G
NP_000268.1:p.Asp143Gly
NP_001341233.1:p.Asp143Gly
NC_000012.11:g.103271253T>C
NM_000277.1:c.428A>G
P00439:p.Asp143Gly

Protein change:

D143G

Links:

UniProtKB: P00439#VAR_000895; dbSNP: rs199475572

NCBI 1000 Genomes Browser:

rs199475572

Molecular consequence:

NM_000277.3:c.428A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354304.2:c.428A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000119512	DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	no classification provided	not provided	not provided	not provided
SCV004222245	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (May 2, 2023)	unknown	clinical testing	PubMed (6) [See all records that cite these PMIDs] 21953985, 18937047, 8889583, 30037505, 32668217, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000119512

DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE

no classification provided

not provided

SCV004222245

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(May 2, 2023)

unknown

clinical testing

PubMed (6)
[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	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Protein stability and in vivo concentration of missense mutations in phenylalanine hydroxylase.

Shi Z, Sellers J, Moult J.

Proteins. 2012 Jan;80(1):61-70. doi: 10.1002/prot.23159. Epub 2011 Sep 21.

PubMed [citation]

PMID:: 21953985
PMCID:: PMC4170182

Biochemical characterization of mutant phenylalanine hydroxylase enzymes and correlation with clinical presentation in hyperphenylalaninaemic patients.

Dobrowolski SF, Pey AL, Koch R, Levy H, Ellingson CC, Naylor EW, Martinez A.

J Inherit Metab Dis. 2009 Feb;32(1):10-21. doi: 10.1007/s10545-008-0942-6. Epub 2008 Oct 21.

PubMed [citation]

PMID:: 18937047

See all PubMed Citations (6)

Details of each submission

From DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE, SCV000119512.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	not provided	not provided

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004222245.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in individuals with classic phenylketonuria (PKU) (PMID: 8889583 (1996)), mild PKU (PMID: 30037505 (2018), 32668217 (2020)), and mild hyperphenylalaninaemia (MPH) (PMID: 18937047 (2009)). Functional studies report this variant results in a damaging effect on PAH protein function (PMID: 8889583 (1996), 18937047 (2009)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, this variant is classified as pathogenic.

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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine