U.S. flag

An official website of the United States government

NM_000277.3(PAH):c.599C>A (p.Thr200Asn) AND Phenylketonuria

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 7, 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:
RCV002260488.1

Allele description [Variation Report for NM_000277.3(PAH):c.599C>A (p.Thr200Asn)]

NM_000277.3(PAH):c.599C>A (p.Thr200Asn)

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.599C>A (p.Thr200Asn)
Other names:
NM_001354304.2:c.599C>A
HGVS:
  • NC_000012.12:g.102855243G>T
  • NG_008690.2:g.108168C>A
  • NM_000277.3:c.599C>AMANE SELECT
  • NM_001354304.2:c.599C>A
  • NP_000268.1:p.Thr200Asn
  • NP_001341233.1:p.Thr200Asn
  • NC_000012.11:g.103249021G>T
Protein change:
T200N
Links:
dbSNP: rs2136649547
NCBI 1000 Genomes Browser:
rs2136649547
Molecular consequence:
  • NM_000277.3:c.599C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354304.2:c.599C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Phenylketonuria (PKU)
Synonyms:
FOLLING DISEASE; OLIGOPHRENIA PHENYLPYRUVICA; Phenylketonurias
Identifiers:
MONDO: MONDO:0009861; MedGen: C0031485; Orphanet: 716; OMIM: 261600

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002540129ClinGen PAH Variant Curation Expert Panel
reviewed by expert panel

(ClinGen PAH ACMG Specifications v1)		Uncertain significance
(Dec 7, 2020) 		germlinecuration

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen PAH Variant Curation Expert Panel, SCV002540129.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

This c.599C>A (p.Thr200Asn) variant in PAH was reported in 1 patient with PAH deficiency referred to as non-PKU HPA (120 - 600uMol/L Phe), detected with pathogenic variant p.Arg243* (PMID: 23357515). Computational evidence for this variant is conflicting; predicted to be damaging (SIFT), disease-causing (MutationTaster) and benign (PolyPhen2). This variant is absent from population databases gnomAD, 1000 Genomes, and ESP. Functional studies have been reported with no major impact on enzyme activity as compared to wild type (PMID: 31208052). In summary, this variant meets criteria to be classified as a variant of 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: Jan 13, 2025