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NM_000277.3(PAH):c.1184C>A (p.Ala395Asp) AND Phenylketonuria

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jul 30, 2022
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:
RCV002509213.1

Allele description [Variation Report for NM_000277.3(PAH):c.1184C>A (p.Ala395Asp)]

NM_000277.3(PAH):c.1184C>A (p.Ala395Asp)

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.1184C>A (p.Ala395Asp)
Other names:
NM_000277.1(PAH):c.1184C>A; p.Ala395Asp
HGVS:
  • NC_000012.12:g.102843661G>T
  • NG_008690.2:g.119750C>A
  • NM_000277.3:c.1184C>AMANE SELECT
  • NM_001354304.2:c.1184C>A
  • NP_000268.1:p.Ala395Asp
  • NP_001341233.1:p.Ala395Asp
  • NC_000012.11:g.103237439G>T
  • NM_000277.1:c.1184C>A
Protein change:
A395D
Links:
dbSNP: rs62508736
NCBI 1000 Genomes Browser:
rs62508736
Molecular consequence:
  • NM_000277.3:c.1184C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354304.2:c.1184C>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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002818508ClinGen PAH Variant Curation Expert Panel
reviewed by expert panel

(ClinGen PAH ACMG Specifications v1)
Likely pathogenic
(Jul 30, 2022)
germlinecuration

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Phenylketonuria mutations in Northern China.

Song F, Qu YJ, Zhang T, Jin YW, Wang H, Zheng XY.

Mol Genet Metab. 2005 Dec;86 Suppl 1:S107-18. Epub 2005 Oct 26.

PubMed [citation]
PMID:
16256386

Details of each submission

From ClinGen PAH Variant Curation Expert Panel, SCV002818508.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)

Description

This c.1184C>A (p.Ala395Asp) variant in PAH was reported in 1 patient with PAH deficiency (>1200 umol/L Phe) (PMID 16256386). This variant was found at an amino acid residue where p.Ala395Pro, a pathogenic missense variant has been seen before. Computational evidence for this missense variant is predicted to be damaging (SIFT), probably damaging (PolyPhen2), and disease-causing (MutationTaster). This variant is absent from population databases ExAC, gnomAD, 1000 Genomes, and ESP. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM5, PP3, PP4

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 21, 2023