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NM_000277.3(PAH):c.143T>C (p.Leu48Ser) AND Inborn genetic diseases

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 20, 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:
RCV002512612.9

Allele description [Variation Report for NM_000277.3(PAH):c.143T>C (p.Leu48Ser)]

NM_000277.3(PAH):c.143T>C (p.Leu48Ser)

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.143T>C (p.Leu48Ser)
Other names:
p.L48S:TTG>TCG
HGVS:
  • NC_000012.12:g.102912816A>G
  • NG_008690.2:g.50595T>C
  • NM_000277.3:c.143T>CMANE SELECT
  • NM_001354304.2:c.143T>C
  • NP_000268.1:p.Leu48Ser
  • NP_000268.1:p.Leu48Ser
  • NP_001341233.1:p.Leu48Ser
  • NC_000012.11:g.103306594A>G
  • NM_000277.1:c.143T>C
  • NM_000277.2(PAH):c.143T>C
  • P00439:p.Leu48Ser
  • c.143T>C (p.Leu48Ser)
Protein change:
L48S; LEU48SER
Links:
UniProtKB: P00439#VAR_000877; OMIM: 612349.0034; dbSNP: rs5030841
NCBI 1000 Genomes Browser:
rs5030841
Molecular consequence:
  • NM_000277.3:c.143T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354304.2:c.143T>C - 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
SCV003561505Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Apr 20, 2021) 		germlineclinical testing

PubMed (10)
[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

The identification of two mis-sense mutations at the PAH gene locus in a Turkish patient with phenylketonuria.

Konecki DS, Schlotter M, Trefz FK, Lichter-Konecki U.

Hum Genet. 1991 Aug;87(4):389-93.

PubMed [citation]
PMID:
1679030

Human phenylalanine hydroxylase mutations and hyperphenylalaninemia phenotypes: a metanalysis of genotype-phenotype correlations.

Kayaalp E, Treacy E, Waters PJ, Byck S, Nowacki P, Scriver CR.

Am J Hum Genet. 1997 Dec;61(6):1309-17.

PubMed [citation]
PMID:
9399896
PMCID:
PMC1716084
See all PubMed Citations (10)

Details of each submission

From Ambry Genetics, SCV003561505.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (10)

Description

The c.143T>C (p.L48S) alteration is located in exon 2 (coding exon 2) of the PAH gene. This alteration results from a T to C substitution at nucleotide position 143, causing the leucine (L) at amino acid position 48 to be replaced by a serine (S). Based on data from the Genome Aggregation Database (gnomAD), the PAH c.143T>C alteration was observed in 0.012% (34/282,822) of total alleles studied, with a frequency of 0.025% (9/35,440) in the Latino subpopulation. This is a recurrent mutation, reported in multiple unrelated patients with mild and classic PKU (Konecki, 1991; Couce, 2013; Djordjevic, 2013; Gundorova, 2019; Su, 2019). This amino acid position is highly conserved in available vertebrate species. Functional analysis of the p.L48S alteration, either homozygous or compound heterozygous with another PAH mutation, found that it is associated with reduced enzyme activity compared to wildtype (Waters, 2001; Danecka, 2015; Shen, 2016). The p.L48S 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