NM_000277.3(PAH):c.941del (p.Pro314fs) AND Phenylketonuria

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 12, 2022
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:: RCV002259597.1

Allele description [Variation Report for NM_000277.3(PAH):c.941del (p.Pro314fs)]

NM_000277.3(PAH):c.941del (p.Pro314fs)

Gene:

PAH:phenylalanine hydroxylase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

12q23.2

Genomic location:

Preferred name:

NM_000277.3(PAH):c.941del (p.Pro314fs)

Other names:

NM_000277.3(PAH):c.941del; p.Pro314fs

HGVS:

NC_000012.12:g.102846924del
NG_008690.2:g.116488del
NM_000277.3:c.941delMANE SELECT
NM_001354304.2:c.941del
NP_000268.1:p.Pro314fs
NP_001341233.1:p.Pro314fs
NC_000012.11:g.103240702del
NM_000277.1:c.940delC

Protein change:

P314fs

Links:

dbSNP: rs62642907

NCBI 1000 Genomes Browser:

rs62642907

Molecular consequence:

NM_000277.3:c.941del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354304.2:c.941del - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002540138	ClinGen PAH Variant Curation Expert Panel	reviewed by expert panel (ClinGen PAH ACMG Specifications v1)	Pathogenic (Jun 12, 2022)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002540138

ClinGen PAH Variant Curation Expert Panel

reviewed by expert panel

(ClinGen PAH ACMG Specifications v1)

Pathogenic
(Jun 12, 2022)

germline

curation

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation

Details of each submission

From ClinGen PAH Variant Curation Expert Panel, SCV002540138.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

The frameshift variant c.941del (HGVS nomenclature c.940del) occurs in exon 9 of 13 and is predicted to result in NMD. The variant is absent from population databases, including gnomAD. One classical PKU patient has been reported (PMID: 9600453) with this variant in trans with c.1066-11G>A (ClinVar 607, Pathogenic with expert panel review). In summary, this variant meets criteria to be classified as Pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PM3, PP4.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jul 7, 2022

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