VCV000255760.31 - ClinVar

NM_000289.6(PFKM):c.299G>A (p.Arg100Gln)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(12)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000289.6(PFKM):c.299G>A (p.Arg100Gln)

Variation ID: 255760 Accession: VCV000255760.31

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 12q13.11 12: 48132929 (GRCh38) [ NCBI UCSC ] 12: 48526712 (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	Oct 3, 2016	Sep 29, 2024	Feb 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000289.6:c.299G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000280.1:p.Arg100Gln	missense
NM_001166686.2:c.512G>A	NP_001160158.1:p.Arg171Gln	missense
NM_001166687.2:c.299G>A	NP_001160159.1:p.Arg100Gln	missense
NM_001166688.2:c.299G>A	NP_001160160.1:p.Arg100Gln	missense
NM_001354735.1:c.608G>A	NP_001341664.1:p.Arg203Gln	missense
NM_001354736.1:c.608G>A	NP_001341665.1:p.Arg203Gln	missense
NM_001354737.1:c.512G>A	NP_001341666.1:p.Arg171Gln	missense
NM_001354738.1:c.512G>A	NP_001341667.1:p.Arg171Gln	missense
NM_001354739.1:c.512G>A	NP_001341668.1:p.Arg171Gln	missense
NM_001354740.1:c.443G>A	NP_001341669.1:p.Arg148Gln	missense
NM_001354741.2:c.323G>A	NP_001341670.1:p.Arg108Gln	missense
NM_001354742.2:c.299G>A	NP_001341671.1:p.Arg100Gln	missense
NM_001354743.2:c.299G>A	NP_001341672.1:p.Arg100Gln	missense
NM_001354744.2:c.299G>A	NP_001341673.1:p.Arg100Gln	missense
NM_001354745.2:c.212G>A	NP_001341674.1:p.Arg71Gln	missense
NM_001354746.2:c.299G>A	NP_001341675.1:p.Arg100Gln	missense
NM_001354747.2:c.149G>A	NP_001341676.1:p.Arg50Gln	missense
NM_001354748.2:c.149G>A	NP_001341677.1:p.Arg50Gln	missense
NM_001363619.2:c.299G>A	NP_001350548.1:p.Arg100Gln	missense
NR_148954.2:n.350G>A		non-coding transcript variant
NR_148955.1:n.1120G>A		non-coding transcript variant
NR_148956.2:n.276G>A		non-coding transcript variant
NR_148957.2:n.350G>A		non-coding transcript variant
NR_148958.2:n.350G>A		non-coding transcript variant
NR_148959.2:n.276G>A		non-coding transcript variant
NC_000012.12:g.48132929G>A
NC_000012.11:g.48526712G>A
NG_016199.2:g.32677G>A
LRG_1177:g.32677G>A
LRG_1177t1:c.299G>A	LRG_1177p1:p.Arg100Gln
	P08237:p.Arg100Gln

... more HGVS ... less HGVS

Protein change

R100Q, R171Q, R50Q, R108Q, R148Q, R203Q, R71Q

Other names

NM_000289.5(PFKM):c.299G>A(p.Arg100Gln)
NM_001166686.1(PFKM):c.512G>A(p.Arg171Gln)
NM_001166687.1(PFKM):c.299G>A(p.Arg100Gln)
NM_001166688.1(PFKM):c.299G>A(p.Arg100Gln)

Canonical SPDI

NC_000012.12:48132928:G:A

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.

0.14776 (A)

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

The Genome Aggregation Database (gnomAD) 0.16379

Trans-Omics for Precision Medicine (TOPMed) 0.16560

1000 Genomes Project 30x 0.14382

1000 Genomes Project 0.14776

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.17192

Exome Aggregation Consortium (ExAC) 0.17778

The Genome Aggregation Database (gnomAD), exomes 0.17814

Links

ClinGen: CA6536961 UniProtKB: P08237#VAR_006065 dbSNP: rs2228500 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.
PFKM		-	-	GRCh38 GRCh37	931	949

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 specified	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	Dec 3, 2021	RCV000245226.11
Glycogen storage disease, type VII	Benign (6)	criteria provided, multiple submitters, no conflicts	Feb 1, 2024	RCV000322166.26
not provided	Likely benign (2)	criteria provided, single submitter	-	RCV000675434.7

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.
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000303490.1 First in ClinVar: Oct 03, 2016 Last updated: Oct 03, 2016
Benign (Jul 17, 2015)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000332947.4 First in ClinVar: Dec 06, 2016 Last updated: Mar 08, 2017	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PFKM Number of individuals with the variant: 1 Sex: mixed
Benign (Mar 06, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Glycogen storage disease, type VII Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000379093.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Benign (Jan 08, 2016)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	not specified Affected status: yes Allele origin: germline	GeneDx Accession: SCV000517627.4 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	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) 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 a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
Benign (May 31, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: curation	Glycogen storage disease, type VII Affected status: unknown Allele origin: unknown	SIB Swiss Institute of Bioinformatics Accession: SCV000803447.1 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016	Comment: This variant is interpreted as a Benign - Stand Alone, for Glycogen storage disease VII, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: … (more) This variant is interpreted as a Benign - Stand Alone, for Glycogen storage disease VII, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BA1 =>Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. (less)
Benign (Jul 01, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Glycogen storage disease, type VII Affected status: no Allele origin: germline	Pars Genome Lab Accession: SCV001750026.1 First in ClinVar: Jul 14, 2021 Last updated: Jul 14, 2021	Sex: mixed
Likely benign (Dec 03, 2021)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV002051233.1 First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Glycogen storage disease, type VII Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001719754.4 First in ClinVar: Jun 15, 2021 Last updated: Feb 20, 2024
Benign (Nov 30, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	Glycogen storage disease, type VII Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000604622.10 First in ClinVar: Aug 05, 2018 Last updated: Feb 20, 2024
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005216748.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Benign (Dec 16, 2015)	no assertion criteria provided Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV000801114.1 First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018
Benign (Sep 16, 2020)	no assertion criteria provided Method: clinical testing	Glycogen storage disease type VII Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV001457679.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021
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Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

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 a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Comment:

This variant is interpreted as a Benign - Stand Alone, for Glycogen storage disease VII, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BA1 =>Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium.

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
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PFKM	-	-	-	-

Text-mined citations for rs2228500 ...

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 Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_000289.6(PFKM):c.299G>A (p.Arg100Gln)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs2228500 ...