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NM_000277.3(PAH):c.43_44insAG (p.Leu15fs) AND Phenylketonuria

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 12, 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:
RCV000993596.1

Allele description [Variation Report for NM_000277.3(PAH):c.43_44insAG (p.Leu15fs)]

NM_000277.3(PAH):c.43_44insAG (p.Leu15fs)

Gene:
PAH:phenylalanine hydroxylase [Gene - OMIM - HGNC]
Variant type:
Insertion
Cytogenetic location:
12q23.2
Genomic location:
Preferred name:
NM_000277.3(PAH):c.43_44insAG (p.Leu15fs)
HGVS:
  • NC_000012.12:g.102917087_102917088insCT
  • NG_008690.2:g.46323_46324insAG
  • NM_000277.3:c.43_44insAGMANE SELECT
  • NM_001354304.2:c.43_44insAG
  • NP_000268.1:p.Leu15fs
  • NP_001341233.1:p.Leu15fs
  • NC_000012.11:g.103310865_103310866insCT
  • NM_000277.1:c.43_44insAG
Protein change:
L15fs
Links:
dbSNP: rs1592991196
NCBI 1000 Genomes Browser:
rs1592991196
Molecular consequence:
  • NM_000277.3:c.43_44insAG - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354304.2:c.43_44insAG - 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
SCV001146687ClinGen PAH Variant Curation Expert Panel
reviewed by expert panel

(ClinGen PAH ACMG Specifications v1)		Pathogenic
(Aug 12, 2019) 		germlinecuration

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

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Five novel mutations and two large deletions in a population analysis of the phenylalanine hydroxylase gene.

Groselj U, Tansek MZ, Kovac J, Hovnik T, Podkrajsek KT, Battelino T.

Mol Genet Metab. 2012 Jun;106(2):142-8. doi: 10.1016/j.ymgme.2012.03.015. Epub 2012 Apr 1.

PubMed [citation]
PMID:
22513348

Details of each submission

From ClinGen PAH Variant Curation Expert Panel, SCV001146687.1

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

Description

The PAH: c.43_44insAG variant is a frameshift variant occurring in exon 1 of 13 in the canonical transcript of PAH, a gene fulfilling the most recent criteria for LOF being a known disease mechanism (see PMID: 30192042) (PVS1). The variant has been reported with the IVS8-2A>G (c.913-2A>G) splice-site variant (PMID: 22513348), a recurrent splice-site variant among Central European PKU cases (see PMID: 23160875) in one Slovenian proband with classic PKU as assessed by plasma Phe levels; BH4 deficiency does not appear to have been formally excluded by biochemical or genetic testing (PP4). It is absent from control databases including ethnically matched individuals, including gnomAD/ExAC, 1000 Genomes, and ESP (PM2).

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

Last Updated: Apr 23, 2022