6-131847856-GGTGTGTGTGTGTGTGTGTGTGTGTGT-GGTGTGTGTGTGTGTGTGTGTGT

Position:

chr6-131847856-GGTGTGTGTGTGTGTGTGTGTGTGTGT-GGTGTGTGTGTGTGTGTGTGTGT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_006208.3(ENPP1):c.313+43_313+46del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0497 in 1,171,032 control chromosomes in the GnomAD database, including 544 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.067 ( 356 hom., cov: 0)

Exomes 𝑓: 0.047 ( 188 hom. )

Consequence

ENPP1
NM_006208.3 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:3

Conservation

PhyloP100: 0.468

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 Benign. Variant got -9 ACMG points.

BP6

Variant 6-131847856-GGTGT-G is Benign according to our data. Variant chr6-131847856-GGTGT-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 355333.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=2, Likely_benign=2}. Variant chr6-131847856-GGTGT-G is described in Lovd as [Benign]. Variant chr6-131847856-GGTGT-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENPP1	NM_006208.3 linkuse as main transcript	c.313+43_313+46del		intron_variant		ENST00000647893.1	NP_006199.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
ENPP1	ENST00000647893.1 linkuse as main transcript	c.313+43_313+46del	intron_variant		NM_006208.3	ENSP00000498074	P1
ENPP1	ENST00000513998.5 linkuse as main transcript	c.313+43_313+46del	intron_variant, NMD_transcript_variant	5		ENSP00000422424
ENPP1	ENST00000650507.1 linkuse as main transcript	c.149+43_149+46del	intron_variant, NMD_transcript_variant			ENSP00000497375
ENPP1	ENST00000486853.1 linkuse as main transcript	n.333+43_333+46del	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0669

AC:

9168

AN:

137026

Hom.:

354

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.0594

Gnomad AMR

AF:

0.0643

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.0186

Gnomad SAS

AF:

0.0123

Gnomad FIN

AF:

0.0760

Gnomad MID

AF:

0.0576

Gnomad NFE

AF:

0.0466

Gnomad OTH

AF:

0.0566

GnomAD4 exome

AF:

0.0474

AC:

49042

AN:

1033918

Hom.:

188

AF XY:

0.0476

AC XY:

24946

AN XY:

523884

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.0777

Gnomad4 ASJ exome

AF:

0.0304

Gnomad4 EAS exome

AF:

0.0231

Gnomad4 SAS exome

AF:

0.0343

Gnomad4 FIN exome

AF:

0.0959

Gnomad4 NFE exome

AF:

0.0445

Gnomad4 OTH exome

AF:

0.0483

GnomAD4 genome

AF:

0.0671

AC:

9195

AN:

137114

Hom.:

356

Cov.:

AF XY:

0.0665

AC XY:

4435

AN XY:

66694

show subpopulations

Gnomad4 AFR

AF:

0.120

Gnomad4 AMR

AF:

0.0647

Gnomad4 ASJ

AF:

0.0210

Gnomad4 EAS

AF:

0.0188

Gnomad4 SAS

AF:

0.0120

Gnomad4 FIN

AF:

0.0760

Gnomad4 NFE

AF:

0.0467

Gnomad4 OTH

AF:

0.0560

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 08, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 21, 2019	- -

Hypophosphatemic Rickets, Recessive

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Arterial calcification, generalized, of infancy, 1

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 07, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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