VCV000013590.5 - ClinVar

NM_006208.3(ENPP1):c.*1043A>G

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Benign
Benign (2)

2 out of 3 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_006208.3(ENPP1):c.*1043A>G

Variation ID: 13590 Accession: VCV000013590.5

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 6q23.2 6: 131891554 (GRCh38) [ NCBI UCSC ] 6: 132212694 (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	Aug 22, 2016	May 31, 2020	Apr 27, 2017

HGVS

Nucleotide	Protein	Molecular consequence
NM_006208.3:c.*1043A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		3 prime UTR
NC_000006.12:g.131891554A>G
NC_000006.11:g.132212694A>G
NG_008206.1:g.88539A>G
LRG_1288:g.88539A>G
LRG_1288t1:c.*1043A>G

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000006.12:131891553:A: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.

0.44529 (A)

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

The Genome Aggregation Database (gnomAD) 0.44163

The Genome Aggregation Database (gnomAD) 0.44199

Trans-Omics for Precision Medicine (TOPMed) 0.48202

1000 Genomes Project 0.55471

1000 Genomes Project 30x 0.56715

Links

ClinGen: CA210804 OMIM: 173335.0007 dbSNP: rs7754561 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.
ENPP1		Gene associated with autosomal recessive phenotype	No evidence available	GRCh38 GRCh37	938	966

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.
Obesity	risk factor (1)	no assertion criteria provided	Feb 1, 2005	RCV000022719.3
Hypophosphatemic rickets, autosomal recessive, 2	Benign (1)	criteria provided, single submitter	Apr 27, 2017	RCV000372927.5
Arterial calcification, generalized, of infancy, 1	Benign (1)	criteria provided, single submitter	Apr 27, 2017	RCV000280683.5

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.	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.
Benign (Apr 27, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Arterial calcification, generalized, of infancy, 1	Illumina Laboratory Services, Illumina Accession: SCV000460238.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: show This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Apr 27, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Hypophosphatemic rickets, autosomal recessive, 2	Illumina Laboratory Services, Illumina Accession: SCV000460237.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: show This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

risk factor (Feb 01, 2005) N Not contributing to aggregate classification	no assertion criteria provided	OBESITY, SUSCEPTIBILITY TO	OMIM Accession: SCV000044008.2 First in ClinVar: Apr 04, 2013 Last updated: Aug 22, 2016	Publications: PubMed (2) PubMed: 14988267‚ 15677494 Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: Meyre et al. (2004) stated that the A-G1044TGA 3-prime SNP of the ENPP1 gene is associated with obesity (601665). The A-G1044TGA SNP is included in … (more) Meyre et al. (2004) stated that the A-G1044TGA 3-prime SNP of the ENPP1 gene is associated with obesity (601665). The A-G1044TGA SNP is included in an isoform specifically expressed in 3 highly insulin-responsive human tissues (pancreatic islet beta cell, adipocyte, and liver). Mice given an adenovirus expression construct expressing this isoform in hepatocytes showed insulin resistance and glucose intolerance (Dong et al., 2005). (less)

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Increased hepatic levels of the insulin receptor inhibitor, PC-1/NPP1, induce insulin resistance and glucose intolerance.	Dong H	Diabetes	2005	PMID: 15677494
A genome-wide scan for childhood obesity-associated traits in French families shows significant linkage on chromosome 6q22.31-q23.2.	Meyre D	Diabetes	2004	PMID: 14988267

Text-mined citations for rs7754561 ...

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 Apr 13, 2026