NM_006208.3:c.240+11597C>T

Variant names:

• chr6-131819872-C-T
• rs943003
• NM_006208.3:c.240+11597C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006208.3(ENPP1):​c.240+11597C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 463,358 control chromosomes in the GnomAD database, including 92,657 homozygotes. 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 0.65 (32212 hom., cov: 31)
  • Exomes 𝑓: 0.62 (60445 hom.)
• Consequence: ENPP1 NM_006208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 9 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]

SELENOKP2 (HGNC:53725): (selenoprotein K pseudogene 2)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

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.240+11597C>T		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.240+11597C>T		intron	N/A	ENSP00000498074.1	P22413
	ENPP1	ENST00000922186.1		c.240+11597C>T		intron	N/A	ENSP00000592245.1
	SELENOKP2	ENST00000407837.2	TSL:6	n.220G>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98061 AN: 151756 Hom.: 32194 Cov.: 31

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.667

GnomAD4 exome AF: 0.617 AC: 192243 AN: 311488 Hom.: 60445 Cov.: 2 AF XY: 0.622 AC XY: 108759 AN XY: 174994

African (AFR) AF: 0.720 AC: 5217 AN: 7248

American (AMR) AF: 0.522 AC: 8993 AN: 17244

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 6001 AN: 9002

East Asian (EAS) AF: 0.824 AC: 10799 AN: 13110

South Asian (SAS) AF: 0.661 AC: 31563 AN: 47720

European-Finnish (FIN) AF: 0.574 AC: 15995 AN: 27858

Middle Eastern (MID) AF: 0.693 AC: 1252 AN: 1806

European-Non Finnish (NFE) AF: 0.598 AC: 102959 AN: 172198

Other (OTH) AF: 0.618 AC: 9464 AN: 15302

GnomAD4 genome AF: 0.646 AC: 98124 AN: 151870 Hom.: 32212 Cov.: 31 AF XY: 0.645 AC XY: 47891 AN XY: 74194

African (AFR) AF: 0.721 AC: 29872 AN: 41426

American (AMR) AF: 0.593 AC: 9042 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2360 AN: 3462

East Asian (EAS) AF: 0.821 AC: 4242 AN: 5168

South Asian (SAS) AF: 0.679 AC: 3271 AN: 4814

European-Finnish (FIN) AF: 0.578 AC: 6073 AN: 10498

Middle Eastern (MID) AF: 0.712 AC: 208 AN: 292

European-Non Finnish (NFE) AF: 0.608 AC: 41276 AN: 67936

Other (OTH) AF: 0.667 AC: 1408 AN: 2110

Alfa AF: 0.531 Hom.: 1630

Bravo AF: 0.646

Asia WGS AF: 0.748 AC: 2599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.59
PhyloP100		-0.067
Mutation Taster		=100/0	polymorphism (auto)

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: rs943003; hg19: chr6-132141012;