VCV002052085.3 - ClinVar

NM_000289.6(PFKM):c.2041G>A (p.Ala681Thr)

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.

(2)

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.

Uncertain significance

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.2041G>A (p.Ala681Thr)

Variation ID: 2052085 Accession: VCV002052085.3

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 12q13.11 12: 48145079 (GRCh38) [ NCBI UCSC ] 12: 48538862 (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	Feb 8, 2023	Feb 4, 2024	Nov 15, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_000289.6:c.2041G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000280.1:p.Ala681Thr	missense
NM_001166686.2:c.2254G>A	NP_001160158.1:p.Ala752Thr	missense
NM_001166687.2:c.2041G>A	NP_001160159.1:p.Ala681Thr	missense
NM_001166688.2:c.2041G>A	NP_001160160.1:p.Ala681Thr	missense
NM_001354735.1:c.2350G>A	NP_001341664.1:p.Ala784Thr	missense
NM_001354736.1:c.2350G>A	NP_001341665.1:p.Ala784Thr	missense
NM_001354737.1:c.2254G>A	NP_001341666.1:p.Ala752Thr	missense
NM_001354738.1:c.2254G>A	NP_001341667.1:p.Ala752Thr	missense
NM_001354739.1:c.2254G>A	NP_001341668.1:p.Ala752Thr	missense
NM_001354740.1:c.2185G>A	NP_001341669.1:p.Ala729Thr	missense
NM_001354741.2:c.2065G>A	NP_001341670.1:p.Ala689Thr	missense
NM_001354742.2:c.2041G>A	NP_001341671.1:p.Ala681Thr	missense
NM_001354743.2:c.2041G>A	NP_001341672.1:p.Ala681Thr	missense
NM_001354744.2:c.2041G>A	NP_001341673.1:p.Ala681Thr	missense
NM_001354745.2:c.1954G>A	NP_001341674.1:p.Ala652Thr	missense
NM_001354746.2:c.1915G>A	NP_001341675.1:p.Ala639Thr	missense
NM_001354747.2:c.1891G>A	NP_001341676.1:p.Ala631Thr	missense
NM_001354748.2:c.1891G>A	NP_001341677.1:p.Ala631Thr	missense
NM_001363619.2:c.1948G>A	NP_001350548.1:p.Ala650Thr	missense
NR_148954.2:n.2344G>A		non-coding transcript variant
NR_148955.1:n.3114G>A		non-coding transcript variant
NR_148956.2:n.2270G>A		non-coding transcript variant
NR_148957.2:n.2499G>A		non-coding transcript variant
NR_148958.2:n.2247G>A		non-coding transcript variant
NR_148959.2:n.2173G>A		non-coding transcript variant
NC_000012.12:g.48145079G>A
NC_000012.11:g.48538862G>A
NG_016199.2:g.44827G>A
LRG_1177:g.44827G>A
LRG_1177t1:c.2041G>A	LRG_1177p1:p.Ala681Thr

... more HGVS ... less HGVS

Protein change

A650T, A681T, A752T, A784T, A631T, A729T, A639T, A652T, A689T

Other names

Canonical SPDI

NC_000012.12:48145078: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.

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

Links

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	926	944

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.
Glycogen storage disease, type VII	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Nov 15, 2022	RCV002932461.5

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.
Uncertain significance (Jul 06, 2022)	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: SCV003260301.1 First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023	Comment: This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 681 of the PFKM protein (p.Ala681Thr). … (more) This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 681 of the PFKM protein (p.Ala681Thr). This variant is present in population databases (rs752255045, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PFKM-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
Uncertain significance (Nov 15, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Glycogen storage disease, type VII Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV003814888.2 First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024

Comment:

This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 681 of the PFKM protein (p.Ala681Thr). This variant is present in population databases (rs752255045, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PFKM-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_000289.6(PFKM):c.2041G>A (p.Ala681Thr)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...