NM_000277.3(PAH):c.935del (p.Gly312fs) 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:: RCV002260493.1

Allele description [Variation Report for NM_000277.3(PAH):c.935del (p.Gly312fs)]

NM_000277.3(PAH):c.935del (p.Gly312fs)

Gene:

PAH:phenylalanine hydroxylase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

12q23.2

Genomic location:

Preferred name:

NM_000277.3(PAH):c.935del (p.Gly312fs)

Other names:

NM_001354304.2:c.933del

HGVS:

NC_000012.12:g.102846931del
NG_008690.2:g.116482del
NM_000277.3:c.935delMANE SELECT
NM_001354304.2:c.935del
NP_000268.1:p.Gly312fs
NP_001341233.1:p.Gly312fs
NC_000012.11:g.103240709del
NC_000012.12:g.102846929del

Protein change:

G312fs

Links:

dbSNP: rs2136639639

NCBI 1000 Genomes Browser:

rs2136639639

Molecular consequence:

NM_000277.3:c.935del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354304.2:c.935del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Phenylketonuria (PKU)
Synonyms:: FOLLING DISEASE; OLIGOPHRENIA PHENYLPYRUVICA; Phenylketonurias
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
SCV002540137	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

SCV002540137

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, SCV002540137.1

#	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.933del occurs in exon 9 of 13 and is predicted to result in NMD. The variant is absent from population databases, including gnomAD. One patient has been reported (PMID: 21307867) with this variant. In summary, this variant meets criteria to be classified as Pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PP4_moderate.

#	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: Apr 7, 2025

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