6-131808069-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_006208.3(ENPP1):c.34C>G(p.Arg12Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000499 in 1,001,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000012 ( 0 hom. )

Consequence

ENPP1
NM_006208.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.127

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09040034).

BP6

Variant 6-131808069-C-G is Benign according to our data. Variant chr6-131808069-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2983301.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENPP1	NM_006208.3 linkuse as main transcript	c.34C>G	p.Arg12Gly	missense_variant	1/25	ENST00000647893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ENPP1	ENST00000647893.1 linkuse as main transcript	c.34C>G	p.Arg12Gly	missense_variant	1/25		NM_006208.3	P1
ENPP1	ENST00000486853.1 linkuse as main transcript	n.54C>G		non_coding_transcript_exon_variant	1/4	2
ENPP1	ENST00000513998.5 linkuse as main transcript	c.34C>G	p.Arg12Gly	missense_variant, NMD_transcript_variant	1/25	5

Frequencies

GnomAD3 genomes

AF:

0.0000281

AC:

AN:

142582

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000762

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000695

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000116

AC:

AN:

858900

Hom.:

Cov.:

AF XY:

0.00000250

AC XY:

AN XY:

399404

show subpopulations

Gnomad4 AFR exome

AF:

0.0000612

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000281

AC:

AN:

142582

Hom.:

Cov.:

AF XY:

0.0000433

AC XY:

AN XY:

69230

show subpopulations

Gnomad4 AFR

AF:

0.0000762

Gnomad4 AMR

AF:

0.0000695

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 24, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

Cadd

Benign

Dann

Benign

0.44

DEOGEN2

Benign

0.26

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.028

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.090

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.030

N;.

REVEL

Benign

0.076

Sift

Benign

0.25

T;.

Sift4G

Benign

0.17

T;.

Polyphen

0.034

B;B

Vest4

0.11

MutPred

0.35

Loss of methylation at R12 (P = 0.0109);Loss of methylation at R12 (P = 0.0109);

MVP

0.40

MPC

0.26

ClinPred

0.062

GERP RS

0.39

Varity_R

0.075

gMVP

0.14

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over