Variant 6-131847856-GGTGTGTGTGTGTGTGTGTGTGTGTGT-GGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_006208.3(ENPP1):c.313+39_313+46dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 0)

Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

ENPP1
NM_006208.3 intron

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.525

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENPP1	NM_006208.3 linkuse as main transcript	c.313+39_313+46dup		intron_variant		ENST00000647893.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
ENPP1	ENST00000647893.1 linkuse as main transcript	c.313+39_313+46dup	intron_variant		NM_006208.3	P1
ENPP1	ENST00000513998.5 linkuse as main transcript	c.313+39_313+46dup	intron_variant, NMD_transcript_variant	5
ENPP1	ENST00000650507.1 linkuse as main transcript	c.149+39_149+46dup	intron_variant, NMD_transcript_variant
ENPP1	ENST00000486853.1 linkuse as main transcript	n.333+39_333+46dup	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00131

AC:

180

AN:

137176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00439

Gnomad EAS

AF:

0.000413

Gnomad SAS

AF:

0.00141

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000298

Gnomad OTH

AF:

0.00272

GnomAD4 exome

AF:

0.000313

AC:

327

AN:

1044650

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

171

AN XY:

529456

show subpopulations

Gnomad4 AFR exome

AF:

0.000806

Gnomad4 AMR exome

AF:

0.000466

Gnomad4 ASJ exome

AF:

0.00238

Gnomad4 EAS exome

AF:

0.0000840

Gnomad4 SAS exome

AF:

0.000382

Gnomad4 FIN exome

AF:

0.000177

Gnomad4 NFE exome

AF:

0.000244

Gnomad4 OTH exome

AF:

0.000353

GnomAD4 genome

AF:

0.00131

AC:

180

AN:

137264

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

AN XY:

66772

show subpopulations

Gnomad4 AFR

AF:

0.00324

Gnomad4 AMR

AF:

0.00151

Gnomad4 ASJ

AF:

0.00439

Gnomad4 EAS

AF:

0.000414

Gnomad4 SAS

AF:

0.00141

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000298

Gnomad4 OTH

AF:

0.00269

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 29, 2021

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with ENPP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 2 of the ENPP1 gene. It does not directly change the encoded amino acid sequence of the ENPP1 protein. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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