VCV000102695.2 - ClinVar

NM_000277.3(PAH):c.479A>C (p.Gln160Pro)

Germline

Reviewed by expert panel

Reviewed by expert panel. Learn more about how ClinVar calculates review status.

Uncertain Significance

for Phenylketonuria

Classification is based on the expert panel submission

Nov 2024 by ClinGen PAH Variant Curation Expert Panel

The classification is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

FDA Recognized Database

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000277.3(PAH):c.479A>C (p.Gln160Pro)

Variation ID: 102695 Accession: VCV000102695.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 12q23.2 12: 102866626 (GRCh38) [ NCBI UCSC ] 12: 103260404 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Mar 19, 2014	Jan 13, 2025	Nov 17, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000277.3:c.479A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000268.1:p.Gln160Pro	missense
NM_001354304.2:c.479A>C	NP_001341233.1:p.Gln160Pro	missense
NC_000012.12:g.102866626T>G
NC_000012.11:g.103260404T>G
NG_008690.2:g.96785A>C
	P00439:p.Gln160Pro

... more HGVS ... less HGVS

Protein change

Q160P

Other names

NM_000277.3(PAH):c.479A>C

Canonical SPDI

NC_000012.12:102866625:T:G

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA229573 UniProtKB: P00439#VAR_000903 dbSNP: rs199475601 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
PAH		Gene associated with autosomal recessive phenotype	No evidence available	GRCh38 GRCh37	1630	1773

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not provided	not provided (1)	no classification provided	-	RCV000088943.1
Phenylketonuria	Uncertain significance (1)	reviewed by expert panel	Nov 17, 2024	RCV004821977.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain Significance (Nov 17, 2024) C Contributing to aggregate classification	reviewed by expert panel (ClinGen PAH ACMG Specifications v1)	Phenylketonuria (Autosomal recessive inheritance)	ClinGen PAH Variant Curation Expert Panel FDA Recognized Database Accession: SCV005442786.1 First in ClinVar: Jan 13, 2025 Last updated: Jan 13, 2025	Other databases https://erepo.clinicalgenome.org… https://erepo.clinicalgenome.org/evrepo/ui/interpretation/8a149ff5-cf7d-4456-928b-27aeece7ef71 Comment: show The c.479A>C (p.Gln160Pro) variant in PAH is reported in a German patient with PAH deficiency (PMID: 12655553); the second allele/genotype was not reported. It is absent from gnomAD. Computational evidence supports a deleterious effect (REVEL=0.668). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2_supporting, PP3, PP4. (less) Observation: 1 Collection method: curation Allele origin: germline Affected status: unknown Observation 1 Collection method: curation Allele origin: germline Affected status: unknown

not provided (-) N Not contributing to aggregate classification	no classification provided	not provided	DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE Accession: SCV000119544.1 First in ClinVar: Mar 19, 2014 Last updated: Mar 19, 2014	Observation: 1 Collection method: not provided Allele origin: not provided Affected status: not provided Observation 1 Collection method: not provided Allele origin: not provided Affected status: not provided

Comment:

The c.479A>C (p.Gln160Pro) variant in PAH is reported in a German patient with PAH deficiency (PMID: 12655553); the second allele/genotype was not reported. It is absent from gnomAD. Computational evidence supports a deleterious effect (REVEL=0.668). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2_supporting, PP3, PP4.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/8a149ff5-cf7d-4456-928b-27aeece7ef71	-	-	-	-

Text-mined citations for rs199475601 ...

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 May 16, 2026