NM_000277.3(PAH):c.1278T>C (p.Asn426=) AND not provided

Germline classification:: Benign (4 submissions)
Last evaluated:: Jan 13, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000088823.5

Allele description [Variation Report for NM_000277.3(PAH):c.1278T>C (p.Asn426=)]

NM_000277.3(PAH):c.1278T>C (p.Asn426=)

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.1278T>C (p.Asn426=)

Other names:

NM_000277.2(PAH):c.1278T>C

HGVS:

NC_000012.12:g.102840437A>G
NG_008690.2:g.122974T>C
NM_000277.3:c.1278T>CMANE SELECT
NM_001354304.2:c.1278T>C
NP_000268.1:p.Asn426=
NP_001341233.1:p.Asn426=
NC_000012.11:g.103234215A>G
NM_000277.1:c.1278T>C
NP_000268.1:p.(=)

Links:

dbSNP: rs59326968

NCBI 1000 Genomes Browser:

rs59326968

Molecular consequence:

NM_000277.3:c.1278T>C - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001354304.2:c.1278T>C - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000119414	DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	no classification provided	not provided	not provided	not provided
SCV000696435	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Jul 31, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] LabCorp Variant Classification Summary - May 2015.docx, Citation Link,
SCV000888342	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Benign (Jan 13, 2021)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 11180595, 26467025
SCV001872489	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Benign (Mar 1, 2019)	germline	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Ten novel mutations in the phenylalanine hydroxylase gene (PAH) observed in Brazilian patients with phenylketonuria.

Acosta AX, Silva WA Jr, Carvalho TM, Zago MA.

Hum Mutat. 2001;17(1):77.

PubMed [citation]

PMID:: 11139255

Mutations of the phenylalanine hydroxylase (PAH) gene in Brazilian patients with phenylketonuria.

Acosta A, Silva W Jr, Carvalho T, Gomes M, Zago M.

Hum Mutat. 2001 Feb;17(2):122-30.

PubMed [citation]

PMID:: 11180595

See all PubMed Citations (3)

Details of each submission

From DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE, SCV000119414.1

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

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000696435.1

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

Description

Variant summary: The PAH c.1278T>C (p.Asn426Asn) variant involves the alteration of a non-conserved nucleotide causing a synonymous change and 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may alter ESE binding. However, these predictions have yet to be confirmed by functional studies. This variant was found in 1666/121610 control chromosomes (104 homozygotes), predominantly in the African cohort at a frequency of 0.14655 (1525/10406). This frequency is about 19 times the estimated maximal expected allele frequency of a pathogenic PAH variant (0.0079057), suggesting this is likely a benign polymorphism found primarily in population(s) of African origin. A publication, Acosta_2001, classifies the variant as a polymorphism, along with multiple clinical diagnostic laboratories classify the variant as "likely benign/benign." Taken together, this variant is classified as benign.

#	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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000888342.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

#	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 GeneDx, SCV001872489.1

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

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

Last Updated: Mar 10, 2024

ClinVar

Relating variation to medicine