Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

NM_000277.3(PAH):c.299A>G (p.His100Arg)

Help
Interpretation:
Uncertain significance​

Review status:
reviewed by expert panel FDA Recognized Database
Submissions:
4 (Most recent: Feb 25, 2019)
Last evaluated:
Aug 10, 2018
Accession:
VCV000306914.3
Variation ID:
306914
Description:
single nucleotide variant
Help

NM_000277.3(PAH):c.299A>G (p.His100Arg)

Allele ID
315838
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
12q23.2
Genomic location
12: 102894788 (GRCh38) GRCh38 UCSC
12: 103288566 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000012.11:g.103288566T>C
NC_000012.12:g.102894788T>C
NM_000277.3:c.299A>G NP_000268.1:p.His100Arg missense
... more HGVS
Protein change
H100R
Other names
NM_000277.2(PAH):c.299A>G
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00031
The Genome Aggregation Database (gnomAD) 0.00013
Exome Aggregation Consortium (ExAC) 0.00025
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00046
Trans-Omics for Precision Medicine (TOPMed) 0.00043
Links
dbSNP: rs148393887
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 4 reviewed by expert panel Aug 10, 2018 RCV000370322.4
Help
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
PAH - - GRCh38
GRCh37
757 784

Submitted interpretations and evidence

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Aug 10, 2018)
reviewed by expert panel
Method: curation
Phenylketonuria
(Autosomal recessive inheritance)
Allele origin: germline
ClinGen PAH Variant Curation Expert Panel,
FDA Recognized Database
Accession: SCV000852112.3
Submitted: (Feb 25, 2019)
Evidence details
Publications
PubMed (1)
Other databases
https://erepo.clinicalgenome.o...
Comment:
PAH-specific ACMG/AMP criteria applied: BP4: In silico overwhelmingly predict benign. REVEL = 0.553; PP4: Detected in a patient with non PKU hyperphe (PMID:11244681); PM3: H100R ... (more)
Uncertain significance
(May 12, 2017)
criteria provided, single submitter
Method: clinical testing
Phenylketonuria
Allele origin: unknown
Counsyl
Accession: SCV000791580.1
Submitted: (Jul 10, 2018)
Evidence details
Publications
PubMed (1)
Uncertain significance
(Oct 31, 2018)
criteria provided, single submitter
Method: clinical testing
Phenylketonuria
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000896234.1
Submitted: (Nov 14, 2018)
Evidence details
Publications
PubMed (1)
DOI: 10.1038/gim.2015.30
Uncertain significance
(Apr 27, 2017)
criteria provided, single submitter
Method: clinical testing
Phenylketonuria
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000375570.3
Submitted: (Feb 01, 2019)
Evidence details
Publications
PubMed (1)
Comment:
The PAH c.299A>G (p.His100Arg) missense variant has been reported in one individual in a compound heterozygous state with a known pathogenic intronic variant (Mallolas et ... (more)

Citations for this variant

Title Author Journal Year Link
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Richards S Genetics in medicine : official journal of the American College of Medical Genetics 2015 PMID: 25741868
[Clinical, biomedical , neurological and molecular study of 11 patients with new mutations in PAH gene]. Mallolas J Revista de neurologia 2000 PMID: 11244681
Mutational spectrum of phenylalanine hydroxylase deficiency in the population resident in Catalonia: genotype-phenotype correlation. Mallolas J Human genetics 1999 PMID: 10598814
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/a445bf0d-e08f-4300-b282-53c974544d50 - - - -

Record last updated Oct 11, 2019