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NM_000277.3(PAH):c.350del (p.Thr117fs) AND Phenylketonuria

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Dec 22, 2018
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:
RCV000106355.3

Allele description [Variation Report for NM_000277.3(PAH):c.350del (p.Thr117fs)]

NM_000277.3(PAH):c.350del (p.Thr117fs)

Gene:
PAH:phenylalanine hydroxylase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
12q23.2
Genomic location:
Preferred name:
NM_000277.3(PAH):c.350del (p.Thr117fs)
HGVS:
  • NC_000012.12:g.102894737del
  • NG_008690.2:g.68674del
  • NM_000277.3:c.350delMANE SELECT
  • NM_001354304.2:c.350del
  • NP_000268.1:p.Thr117fs
  • NP_001341233.1:p.Thr117fs
  • NC_000012.11:g.103288515del
  • NC_000012.12:g.102894737delG
  • NM_000277.1:c.350delC
  • NM_000277.2(PAH):c.350delC
  • p.Thr117Lysfs
Protein change:
T117fs
Links:
dbSNP: rs281865428
NCBI 1000 Genomes Browser:
rs281865428
Molecular consequence:
  • NM_000277.3:c.350del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354304.2:c.350del - 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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000143854Inserm U 954, Faculté de Médecine de Nancy
no assertion criteria provided
probable-pathogenicunknownnot provided

SCV001146721ClinGen PAH Variant Curation Expert Panel
reviewed by expert panel

(ClinGen PAH ACMG Specifications v1)
Pathogenic
(Dec 22, 2018)
germlinecuration

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration
not providednot providednot providednot providednot providednot provided1not providedliterature only

Citations

PubMed

A mutation analysis of the phenylalanine hydroxylase (PAH) gene in the Israeli population.

Bercovich D, Elimelech A, Yardeni T, Korem S, Zlotogora J, Gal N, Goldstein N, Vilensky B, Segev R, Avraham S, Loewenthal R, Schwartz G, Anikster Y.

Ann Hum Genet. 2008 May;72(Pt 3):305-9. doi: 10.1111/j.1469-1809.2007.00425.x. Epub 2008 Feb 19.

PubMed [citation]
PMID:
18294361

Genotype-phenotype correlations analysis of mutations in the phenylalanine hydroxylase (PAH) gene.

Bercovich D, Elimelech A, Zlotogora J, Korem S, Yardeni T, Gal N, Goldstein N, Vilensky B, Segev R, Avraham S, Loewenthal R, Schwartz G, Anikster Y.

J Hum Genet. 2008;53(5):407-418. doi: 10.1007/s10038-008-0264-4. Epub 2008 Feb 26.

PubMed [citation]
PMID:
18299955

Details of each submission

From Inserm U 954, Faculté de Médecine de Nancy, SCV000143854.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providednot providednot provided

Description

Converted during submission to Likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownnot provided1not providednot providednot providednot providednot providednot provided

From ClinGen PAH Variant Curation Expert Panel, SCV001146721.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (2)

Description

The c.350delC variant in PAH has been previously reported in at least 2 Arab-Israeli probands with classic PKU (PMID: 18299955; PMID: 18294361); BH4 deficiency was not excluded (PP4). The variant is a frameshift variant occurring in exon 3 of 13 in the canonical transcript of PAH, a gene fulfilling the most recent criteria for LOF being a known disease mechanism (PVS1; see PVS1: Recommendations for Interpreting the Loss of Function PVS1 ACMG/AMP Variant Criteria). It is absent from control databases including ethnically matched individuals, including gnomAD/ExAC, 1000 Genomes, and the Greater Middle East Variome (PM2).

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

Last Updated: Jun 23, 2024