VCV000102906.2 - ClinVar

NM_000277.3(PAH):c.941del (p.Pro314fs)

Germline

Top reviewed classifications are shown here.

Submission summary:

2 submissions

2 submitters

2 conditions

Reviewed by expert panel

Pathogenic

Jun 2022 by ClinGen PAH Va… FDA Recognized Database

for Phenylketonuria

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000277.3(PAH):c.941del (p.Pro314fs)

Variation ID: 102906 Accession: VCV000102906.2

Type and length

Deletion, 1 bp

Location

Cytogenetic: 12q23.2 12: 102846923 (GRCh38) [ NCBI UCSC ] 12: 103240701 (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	Jul 2, 2022	Jun 12, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_000277.3:c.941del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000268.1:p.Pro314fs	frameshift
NM_001354304.2:c.941del	NP_001341233.1:p.Pro314fs	frameshift
NC_000012.12:g.102846924del
NC_000012.11:g.103240702del
NG_008690.2:g.116488del

... more HGVS ... less HGVS

Protein change

P314fs

Other names

NM_000277.3(PAH):c.941del
p.Pro314fs

Canonical SPDI

NC_000012.12:102846922:GG:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

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: CA229866 dbSNP: rs62642907 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		-	-	GRCh38 GRCh37	1506	1629

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	-	RCV000089170.1
Phenylketonuria	Pathogenic (1)	reviewed by expert panel	Jun 12, 2022	RCV002259597.1

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.	More information 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.
Pathogenic (Jun 12, 2022)	reviewed by expert panel (ClinGen PAH ACMG Specifications v1) Method: curation	Phenylketonuria (Autosomal recessive inheritance) Affected status: unknown Allele origin: germline	ClinGen PAH Variant Curation Expert Panel FDA Recognized Database Accession: SCV002540138.1 First in ClinVar: Jul 02, 2022 Last updated: Jul 02, 2022	Other databases https://erepo.clinicalgenome.org… https://erepo.clinicalgenome.org/evrepo/ui/interpretation/e27280b9-e470-4ae1-a0ea-56e2782d634d Comment: The frameshift variant c.941del (HGVS nomenclature c.940del) occurs in exon 9 of 13 and is predicted to result in NMD. The variant is absent from … (more) The frameshift variant c.941del (HGVS nomenclature c.940del) occurs in exon 9 of 13 and is predicted to result in NMD. The variant is absent from population databases, including gnomAD. One classical PKU patient has been reported (PMID: 9600453) with this variant in trans with c.1066-11G>A (ClinVar 607, Pathogenic with expert panel review). In summary, this variant meets criteria to be classified as Pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PM3, PP4. (less)
not provided (-)	no classification provided Method: not provided	not provided Affected status: not provided Allele origin: not provided	DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE Accession: SCV000119785.1 First in ClinVar: Mar 19, 2014 Last updated: Mar 19, 2014

Comment:

The frameshift variant c.941del (HGVS nomenclature c.940del) occurs in exon 9 of 13 and is predicted to result in NMD. The variant is absent from population databases, including gnomAD. One classical PKU patient has been reported (PMID: 9600453) with this variant in trans with c.1066-11G>A (ClinVar 607, Pathogenic with expert panel review). In summary, this variant meets criteria to be classified as Pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PM3, PP4.

Germline Functional Evidence

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.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/e27280b9-e470-4ae1-a0ea-56e2782d634d	-	-	-	-

Text-mined citations for rs62642907 ...

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 Jul 09, 2022

ClinVar Genomic variation as it relates to human health

NM_000277.3(PAH):c.941del (p.Pro314fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs62642907 ...