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NM_000277.3(PAH):c.117C>G (p.Phe39Leu) AND Inborn genetic diseases

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 6, 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:
RCV004018527.1

Allele description [Variation Report for NM_000277.3(PAH):c.117C>G (p.Phe39Leu)]

NM_000277.3(PAH):c.117C>G (p.Phe39Leu)

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.117C>G (p.Phe39Leu)
Other names:
p.F39L:TTC>TTG
HGVS:
  • NC_000012.12:g.102912842G>C
  • NG_008690.2:g.50569C>G
  • NM_000277.3:c.117C>GMANE SELECT
  • NM_001354304.2:c.117C>G
  • NP_000268.1:p.Phe39Leu
  • NP_000268.1:p.Phe39Leu
  • NP_001341233.1:p.Phe39Leu
  • NC_000012.11:g.103306620G>C
  • NM_000277.1:c.117C>G
  • NM_000277.3(PAH):c.117C>GMANE SELECT
  • P00439:p.Phe39Leu
  • c.117C>G (p.Phe39Leu)
Protein change:
F39L; PHE39LEU
Links:
UniProtKB: P00439#VAR_000870; OMIM: 612349.0031; dbSNP: rs62642926
NCBI 1000 Genomes Browser:
rs62642926
Molecular consequence:
  • NM_000277.3:c.117C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354304.2:c.117C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004998564Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Dec 6, 2023) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mutation detection in phenylketonuria by using chemical cleavage of mismatch: importance of using probes from both normal and patient samples.

Forrest SM, Dahl HH, Howells DW, Dianzani I, Cotton RG.

Am J Hum Genet. 1991 Jul;49(1):175-83. Erratum in: Am J Hum Genet 1992 Mar;50(3):659.

PubMed [citation]
PMID:
2063869
PMCID:
PMC1683212

Discordant phenylketonuria phenotypes in one family: the relationship between genotype and clinical outcome is a function of multiple effects.

Tyfield LA, Zschocke J, Stephenson A, Cockburn F, Harvie A, Bidwell JL, Wood NA, Hunt LP.

J Med Genet. 1995 Nov;32(11):867-70.

PubMed [citation]
PMID:
8592329
PMCID:
PMC1051737
See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV004998564.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

The c.117C>G (p.F39L) alteration is located in exon 2 (coding exon 2) of the PAH gene. This alteration results from a C to G substitution at nucleotide position 117, causing the phenylalanine (F) at amino acid position 39 to be replaced by a leucine (L). Based on data from gnomAD, the G allele has an overall frequency of 0.009% (26/282820) total alleles studied. The highest observed frequency was 0.016% (21/129140) of European (non-Finnish) alleles. This variant has been reported homozygous or with a second variant in PAH in multiple individuals diagnosed with phenylalanine hydroxylase deficiency (Forrest, 1991; Tyfield, 1995; Koch, 2005; Ho, 2014; Bayat, 2016; Ferreira, 2021). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic.

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

Last Updated: Nov 3, 2024