NM_000277.3(PAH):c.472C>T (p.Arg158Trp) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 22, 2021
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:: RCV000088941.3

Allele description [Variation Report for NM_000277.3(PAH):c.472C>T (p.Arg158Trp)]

NM_000277.3(PAH):c.472C>T (p.Arg158Trp)

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.472C>T (p.Arg158Trp)

Other names:

NM_000277.2(PAH):c.472C>T

HGVS:

NC_000012.12:g.102866633G>A
NG_008690.2:g.96778C>T
NM_000277.3:c.472C>TMANE SELECT
NM_001354304.2:c.472C>T
NP_000268.1:p.Arg158Trp
NP_001341233.1:p.Arg158Trp
NC_000012.11:g.103260411G>A
NC_000012.11:g.103260411G>A
NM_000277.1:c.472C>T
P00439:p.Arg158Trp

Protein change:

R158W

Links:

UniProtKB: P00439#VAR_000902; dbSNP: rs75166491

NCBI 1000 Genomes Browser:

rs75166491

Molecular consequence:

NM_000277.3:c.472C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354304.2:c.472C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Homo sapiens N-acylsphingosine amidohydrolase 2 (ASAH2), transcript variant 1, m...
Homo sapiens N-acylsphingosine amidohydrolase 2 (ASAH2), transcript variant 1, mRNA
gi|1229030994|ref|NM_019893.3|

Nucleotide
Gm16471 predicted gene 16471 [Mus musculus]
Gm16471 predicted gene 16471 [Mus musculus]
Gene ID:105246639

Gene
Gm16471 AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000119541	DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	no classification provided	not provided	not provided	not provided
SCV000581901	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Nov 22, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000119541

DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE

no classification provided

not provided

SCV000581901

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Nov 22, 2021)

germline

clinical testing

Citation Link

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	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE, SCV000119541.1

#	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 GeneDx, SCV000581901.5

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

Description

Reported homozygous in an individual with mild-moderate PKU (Jeannesson-Thivisol et al., 2015); however, this variant has also been identified in individuals with classic PKU (Yamashita et al., 1992; Bashyam et al., 2014; Jeannesson-Thivisol et al., 2015; Danecka et al., 2015); Published functional studies demonstrate p.(R158W) results in significantly reduced residual activity compared to wildtype (Danecka et al., 2015); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25750018, 34828281, 29413232, 25087612, 25596310, 1307609, 26666653, 24130151, 29499199, 30747360, 30275481, 32668217, 32778825, 33375644, 17935162, 17924342)

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

Last Updated: Sep 29, 2024

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