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

Clinical significance:Benign (Last evaluated: Mar 1, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000088823.2

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)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000119414DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTEno assertion providednot providednot providednot provided

SCV000696435Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Benign
(Jul 31, 2017)
germlineclinical testing

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

LabCorp Variant Classification Summary - May 2015.docx,

Citation Link,

SCV000888342Quest Diagnostics Nichols Institute San Juan Capistranocriteria provided, single submitter
Benign
(Oct 13, 2016)
germlineclinical testing

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

SCV001872489GeneDxcriteria provided, single submitter
Benign
(Mar 1, 2019)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providednot providednot providednot providednot providednot provided1not providedliterature only

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

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]
PMID:
26467025
PMCID:
PMC4737317

Details of each submission

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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providednot providednot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1not providednot provided1not providednot providednot providednot providednot providednot provided

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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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.

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000888342.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From GeneDx, SCV001872489.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 18, 2021

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