NM_000277.3(PAH):c.1027T>A (p.Tyr343Asn) AND Phenylketonuria

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 18, 2020
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:: RCV001199981.1

Allele description [Variation Report for NM_000277.3(PAH):c.1027T>A (p.Tyr343Asn)]

NM_000277.3(PAH):c.1027T>A (p.Tyr343Asn)

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.1027T>A (p.Tyr343Asn)

HGVS:

NC_000012.12:g.102844374A>T
NG_008690.2:g.119037T>A
NM_000277.3:c.1027T>AMANE SELECT
NM_001354304.2:c.1027T>A
NP_000268.1:p.Tyr343Asn
NP_001341233.1:p.Tyr343Asn
NC_000012.11:g.103238152A>T

Protein change:

Y343N

Links:

dbSNP: rs62508651

NCBI 1000 Genomes Browser:

rs62508651

Molecular consequence:

NM_000277.3:c.1027T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354304.2:c.1027T>A - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001370808	ClinGen PAH Variant Curation Expert Panel	reviewed by expert panel (ClinGen PAH ACMG Specifications v1)	Likely pathogenic (Jun 18, 2020)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001370808

ClinGen PAH Variant Curation Expert Panel

reviewed by expert panel

(ClinGen PAH ACMG Specifications v1)

Likely pathogenic
(Jun 18, 2020)

germline

curation

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

Citation Link

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	curation

Citations

PubMed

Long-term beneficial effects of the phenylalanine-restricted diet in late-diagnosed individuals with phenylketonuria.

Koch R, Moseley K, Ning J, Romstad A, Guldberg P, Guttler F.

Mol Genet Metab. 1999 Jun;67(2):148-55.

PubMed [citation]

PMID:: 10356314

Details of each submission

From ClinGen PAH Variant Curation Expert Panel, SCV001370808.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (1)

Description

The c.1027T>A (p.Tyr343Asn) variant in PAH has been reported in multiple individuals with PKU (PMID: 10356314) detected with pathogenic variants p.R158Q and p.E280K. This variant is absent in population databases. Computational evidence supports a deleterious effect. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM3, PP3, PP4.

#	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: Apr 23, 2022

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