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NM_000277.3(PAH):c.137del (p.Gly46fs) AND Phenylketonuria

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 3, 2019
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:
RCV000993607.1

Allele description [Variation Report for NM_000277.3(PAH):c.137del (p.Gly46fs)]

NM_000277.3(PAH):c.137del (p.Gly46fs)

Gene:
PAH:phenylalanine hydroxylase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
12q23.2
Genomic location:
Preferred name:
NM_000277.3(PAH):c.137del (p.Gly46fs)
HGVS:
  • NC_000012.12:g.102912823del
  • NG_008690.2:g.50589del
  • NM_000277.3:c.137delMANE SELECT
  • NM_001354304.2:c.137del
  • NP_000268.1:p.Gly46fs
  • NP_001341233.1:p.Gly46fs
  • NC_000012.11:g.103306601del
  • NC_000012.12:g.102912822delC
  • NM_000277.1:c.137delG
  • NM_000277.2(PAH):c.137delG
  • p.Gly46Valfs
Protein change:
G46fs
Links:
dbSNP: rs199475591
NCBI 1000 Genomes Browser:
rs199475591
Molecular consequence:
  • NM_000277.3:c.137del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354304.2:c.137del - frameshift variant - [Sequence Ontology: SO:0001589]

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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001146708ClinGen PAH Variant Curation Expert Panel
reviewed by expert panel

(ClinGen PAH ACMG Specifications v1)		Pathogenic
(Apr 3, 2019) 		germlinecuration

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Haplotypes and mutations of the PAH locus in Egyptian families with PKU.

Effat L, Kuzmin A, Kasem N, Meguid NA, Kotb S, Eisensmith RC, Temtamy SA, Rushdi S, Woo S, el-Awady M.

Eur J Hum Genet. 1999 Feb-Mar;7(2):259-62.

PubMed [citation]
PMID:
10196714

Details of each submission

From ClinGen PAH Variant Curation Expert Panel, SCV001146708.1

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

Description

The c.137delG (p.Gly46Vfs*15) is a frameshift in exon 2 of 13 in PAH, predicted to undergo nonsense mediated decay with the truncated region critical to protein function. It has been reported in 1 individual with PKU (BH4 deficiency not excluded), who carried a second splicing variant (PP4; PMID: 10196714 ). This variant is absent from population databases (PM2). In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PP4.

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

Last Updated: Apr 23, 2022