6-131847856-GGTGTGTGTGT-G

Variant names:

• chr6-131847856-GGTGTGTGTGT-G
• rs59956343
• NM_006208.3:c.313+37_313+46delGTGTGTGTGT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006208.3(ENPP1):​c.313+37_313+46delGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,181,986 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: ENPP1 NM_006208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.721
• Publications: 2 publications found

Genes affected

ENPP1 (HGNC:3356): (ectonucleotide pyrophosphatase/phosphodiesterase 1) This gene is a member of the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family. The encoded protein is a type II transmembrane glycoprotein comprising two identical disulfide-bonded subunits. This protein has broad specificity and cleaves a variety of substrates, including phosphodiester bonds of nucleotides and nucleotide sugars and pyrophosphate bonds of nucleotides and nucleotide sugars. This protein may function to hydrolyze nucleoside 5' triphosphates to their corresponding monophosphates and may also hydrolyze diadenosine polyphosphates. Mutations in this gene have been associated with 'idiopathic' infantile arterial calcification, ossification of the posterior longitudinal ligament of the spine (OPLL), and insulin resistance. [provided by RefSeq, Jul 2008]

ENPP1 Gene-Disease associations (from GenCC):

• arterial calcification, generalized, of infancy, 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• hypopigmentation-punctate palmoplantar keratoderma syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• hypophosphatemic rickets, autosomal recessive, 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• arterial calcification of infancy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive hypophosphatemic rickets

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive inherited pseudoxanthoma elasticum

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006208.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENPP1	NM_006208.3	MANE Select	c.313+37_313+46delGTGTGTGTGT		intron	N/A	NP_006199.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENPP1	ENST00000647893.1	MANE Select	c.313+9_313+18delGTGTGTGTGT		intron	N/A	ENSP00000498074.1
	ENPP1	ENST00000486853.1	TSL:2	n.333+9_333+18delGTGTGTGTGT		intron	N/A
	ENPP1	ENST00000513998.5	TSL:5	n.313+9_313+18delGTGTGTGTGT		intron	N/A	ENSP00000422424.1

Frequencies

GnomAD3 genomes AF: 0.0000656 AC: 9 AN: 137176 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000854

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000721

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000784

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000149 AC: 156 AN: 1044810 Hom.: 0 AF XY: 0.000119 AC XY: 63 AN XY: 529544

African (AFR) AF: 0.000424 AC: 10 AN: 23586

American (AMR) AF: 0.0000517 AC: 2 AN: 38668

Ashkenazi Jewish (ASJ) AF: 0.0000495 AC: 1 AN: 20216

East Asian (EAS) AF: 0.000196 AC: 7 AN: 35694

South Asian (SAS) AF: 0.0000990 AC: 7 AN: 70728

European-Finnish (FIN) AF: 0.0000253 AC: 1 AN: 39558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3112

European-Non Finnish (NFE) AF: 0.000159 AC: 122 AN: 767904

Other (OTH) AF: 0.000132 AC: 6 AN: 45344

GnomAD4 genome AF: 0.0000656 AC: 9 AN: 137176 Hom.: 0 Cov.: 0 AF XY: 0.0000900 AC XY: 6 AN XY: 66674

African (AFR) AF: 0.0000854 AC: 3 AN: 35120

American (AMR) AF: 0.0000721 AC: 1 AN: 13870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2958

East Asian (EAS) AF: 0.00 AC: 0 AN: 4844

South Asian (SAS) AF: 0.00 AC: 0 AN: 4250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.0000784 AC: 5 AN: 63810

Other (OTH) AF: 0.00 AC: 0 AN: 1840

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs59956343; hg19: chr6-132168996;