NM_000277.3(PAH):c.379G>A (p.Glu127Lys) AND Phenylketonuria

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 10, 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:: RCV000664540.2

Allele description [Variation Report for NM_000277.3(PAH):c.379G>A (p.Glu127Lys)]

NM_000277.3(PAH):c.379G>A (p.Glu127Lys)

Gene:

PAH:phenylalanine hydroxylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q23.2

Genomic location:

Preferred name:

NM_000277.3(PAH):c.379G>A (p.Glu127Lys)

HGVS:

NC_000012.12:g.102877524C>T
NG_008690.2:g.85887G>A
NM_000277.3:c.379G>AMANE SELECT
NM_001354304.2:c.379G>A
NP_000268.1:p.Glu127Lys
NP_001341233.1:p.Glu127Lys
NC_000012.11:g.103271302C>T
NM_000277.1:c.379G>A
NM_000277.3(PAH):c.379G>AMANE SELECT
p.Glu127Lys

Protein change:

E127K

Links:

dbSNP: rs1555206565

NCBI 1000 Genomes Browser:

rs1555206565

Molecular consequence:

NM_000277.3:c.379G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354304.2:c.379G>A - missense variant - [Sequence Ontology: SO:0001583]

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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Homo sapiens secretin (SCT), mRNA
Homo sapiens secretin (SCT), mRNA
gi|11345449|ref|NM_021920.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000788519	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Jan 11, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV001250524	ClinGen PAH Variant Curation Expert Panel	reviewed by expert panel (ClinGen PAH ACMG Specifications v1)	Uncertain significance (Nov 10, 2019)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000788519

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Uncertain significance
(Jan 11, 2017)

unknown

clinical testing

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

Citation Link,

SCV001250524

ClinGen PAH Variant Curation Expert Panel

reviewed by expert panel

(ClinGen PAH ACMG Specifications v1)

Uncertain significance
(Nov 10, 2019)

germline

curation

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

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular characterisation of phenylketonuria in a Chinese mainland population using next-generation sequencing.

Li N, Jia H, Liu Z, Tao J, Chen S, Li X, Deng Y, Jin X, Song J, Zhang L, Liang Y, Wang W, Zhu J.

Sci Rep. 2015 Oct 27;5:15769. doi: 10.1038/srep15769.

PubMed [citation]

PMID:: 26503515
PMCID:: PMC4621502

Details of each submission

From Counsyl, SCV000788519.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

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

From ClinGen PAH Variant Curation Expert Panel, SCV001250524.1

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

Description

The c.379G>A (p.Glu127Lys) variant in PAH has been reported in a patient with PAH deficiency (BH4 deficiency excluded) (PP4_Moderate; PMID: 26503515) This variant is absent from 1000G, ESP, ExAC and gnomAD (PM2). A deleterious effect is predicted in SIFT, Polyphen-2 HVAR, MutationTaster, and REVEL=0.781. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PP3.

#	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 23, 2022

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