6-131847857-G-A

Variant names:

• chr6-131847857-G-A
• rs7773477
• NM_006208.3:c.313+9G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006208.3(ENPP1):​c.313+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: ENPP1 NM_006208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.525
• Publications: 5 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, ClinGen
• hypopigmentation-punctate palmoplantar keratoderma syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: ClinGen, G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENPP1	NM_006208.3	MANE Select	c.313+9G>A		intron	N/A	NP_006199.2	P22413

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENPP1	ENST00000647893.1	MANE Select	c.313+9G>A		intron	N/A	ENSP00000498074.1	P22413
	ENPP1	ENST00000922186.1		c.313+9G>A		intron	N/A	ENSP00000592245.1
	ENPP1	ENST00000486853.1	TSL:2	n.333+9G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000851 AC: 3 AN: 35236 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000976

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000179 AC: 2 AN: 111610 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000404

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000151 AC: 50 AN: 330306 Hom.: 0 Cov.: 14 AF XY: 0.000156 AC XY: 26 AN XY: 166852

African (AFR) AF: 0.00 AC: 0 AN: 8208

American (AMR) AF: 0.000181 AC: 2 AN: 11060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7396

East Asian (EAS) AF: 0.00 AC: 0 AN: 6926

South Asian (SAS) AF: 0.00 AC: 0 AN: 20516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7996

Middle Eastern (MID) AF: 0.00183 AC: 2 AN: 1094

European-Non Finnish (NFE) AF: 0.000173 AC: 44 AN: 253676

Other (OTH) AF: 0.000149 AC: 2 AN: 13434

GnomAD4 genome AF: 0.0000851 AC: 3 AN: 35236 Hom.: 0 Cov.: 0 AF XY: 0.0000607 AC XY: 1 AN XY: 16474

African (AFR) AF: 0.0000976 AC: 1 AN: 10250

American (AMR) AF: 0.00 AC: 0 AN: 2968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 874

East Asian (EAS) AF: 0.00 AC: 0 AN: 1170

South Asian (SAS) AF: 0.00 AC: 0 AN: 808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 80

European-Non Finnish (NFE) AF: 0.000118 AC: 2 AN: 16954

Other (OTH) AF: 0.00 AC: 0 AN: 514

Alfa AF: 0.00 Hom.: 327

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.89
DANN	Benign	0.60
PhyloP100		-0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7773477; hg19: chr6-132168997;