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NM_000277.3(PAH):c.963C>T (p.Leu321=)

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Interpretation:
Benign​

Review status:
reviewed by expert panel FDA Recognized Database
Submissions:
8 (Most recent: Jan 7, 2021)
Last evaluated:
Jul 29, 2018
Accession:
VCV000102911.7
Variation ID:
102911
Description:
single nucleotide variant
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NM_000277.3(PAH):c.963C>T (p.Leu321=)

Allele ID
108647
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
12q23.2
Genomic location
12: 102846901 (GRCh38) GRCh38 UCSC
12: 103240679 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000012.11:g.103240679G>A
NC_000012.12:g.102846901G>A
NG_008690.2:g.116510C>T
... more HGVS
Protein change
-
Other names
NM_000277.2(PAH):c.963C>T
Canonical SPDI
NC_000012.12:102846900:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
0.01438 (A)

Allele frequency
The Genome Aggregation Database (gnomAD) 0.01486
The Genome Aggregation Database (gnomAD) 0.01582
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01753
1000 Genomes Project 0.01438
Trans-Omics for Precision Medicine (TOPMed) 0.01668
Trans-Omics for Precision Medicine (TOPMed) 0.01670
Links
ClinGen: CA229873
dbSNP: rs61747292
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Benign 4 reviewed by expert panel Jul 29, 2018 RCV000721181.5
Benign 3 criteria provided, multiple submitters, no conflicts Jun 17, 2019 RCV000507684.3
not provided 1 no assertion provided - RCV000089175.3
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
PAH - - GRCh38
GRCh37
1115 1145

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Benign
(Jul 29, 2018)
reviewed by expert panel
Method: curation
Phenylketonuria
(Autosomal recessive inheritance)
Allele origin: germline
ClinGen PAH Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV000852147.3
Submitted: (Feb 25, 2019)
Evidence details
Other databases
https://erepo.clinicalgenome.org…
Comment:
PAH-specific ACMG/AMP criteria applied: BS1: >0.02% as set by the PAH specific specifications; BP7: ; BS3_Supporting: cDNA method demonstrates 98% and intinic system demonstrates 81% … (more)
Benign
(Oct 12, 2016)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000601720.1
Submitted: (Aug 01, 2017)
Evidence details
Publications
PubMed (7)
Benign
(Feb 27, 2018)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
GeneDx
Accession: SCV000729359.1
Submitted: (Mar 26, 2018)
Evidence details
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
Likely benign
(Apr 27, 2017)
criteria provided, single submitter
Method: clinical testing
Phenylketonuria
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV001271162.1
Submitted: (Feb 20, 2020)
Evidence details
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
Benign
(Jun 17, 2019)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001361062.1
Submitted: (Mar 06, 2020)
Evidence details
Comment:
Variant summary: PAH c.963C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these … (more)
Benign
(Nov 28, 2020)
criteria provided, single submitter
Method: clinical testing
Phenylketonuria
Allele origin: germline
Invitae
Accession: SCV001012192.3
Submitted: (Jan 07, 2021)
Evidence details
Benign
(Sep 16, 2020)
no assertion criteria provided
Method: clinical testing
Phenylketonuria
Allele origin: germline
Natera, Inc.
Accession: SCV001463128.1
Submitted: (Dec 28, 2020)
Evidence details
not provided
(-)
no assertion provided
Method: not provided
not provided
Allele origin: not provided
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE
Accession: SCV000119790.1
Submitted: (Mar 30, 2012)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Mutation spectrum of phenylketonuria in Syrian population: genotype-phenotype correlation. Murad H Gene 2013 PMID: 23856132
Convergent patterns of association between phenylalanine hydroxylase variants and schizophrenia in four independent samples. Talkowski ME American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2009 PMID: 18937293
Simultaneous assessment of the effects of exonic mutations on RNA splicing and protein functions. Ho PY Biochemical and biophysical research communications 2008 PMID: 18590700
Investigation of the phenylalanine hydroxylase gene and tardive dyskinesia. Richardson MA American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 2006 PMID: 16402341
Phenylalanine hydroxylase gene in psychiatric patients: screening and functional assay of mutations. Richardson MA Biological psychiatry 2003 PMID: 12644360
Aromatic amino acid hydroxylase genes and schizophrenia. Chao HM American journal of medical genetics 2002 PMID: 12210276
Ten novel mutations in the phenylalanine hydroxylase gene (PAH) observed in Brazilian patients with phenylketonuria. Acosta AX Human mutation 2001 PMID: 11139255
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/31e57f08-7be8-46c7-902d-8429b753f57c - - - -

Text-mined citations for rs61747292...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 27, 2021