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

Variant summary

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

The NM_006208.3(ENPP1):c.313+41_313+46del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00757 in 1,180,416 control chromosomes in the GnomAD database, including 74 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.020 ( 64 hom., cov: 0)

Exomes 𝑓: 0.0060 ( 10 hom. )

Consequence

ENPP1
NM_006208.3 intron

Scores

Not classified

Clinical Significance

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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 6-131847856-GGTGTGT-G is Benign according to our data. Variant chr6-131847856-GGTGTGT-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 355334.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=2, Likely_benign=1}. Variant chr6-131847856-GGTGTGT-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0647 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+41_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+41_313+46del	intron_variant		NM_006208.3	ENSP00000498074	P1
ENPP1	ENST00000513998.5 linkuse as main transcript	c.313+41_313+46del	intron_variant, NMD_transcript_variant	5		ENSP00000422424
ENPP1	ENST00000650507.1 linkuse as main transcript	c.149+41_149+46del	intron_variant, NMD_transcript_variant			ENSP00000497375
ENPP1	ENST00000486853.1 linkuse as main transcript	n.333+41_333+46del	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0194

AC:

2664

AN:

137130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0668

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00743

Gnomad ASJ

AF:

0.00203

Gnomad EAS

AF:

0.00145

Gnomad SAS

AF:

0.00212

Gnomad FIN

AF:

0.000962

Gnomad MID

AF:

0.00719

Gnomad NFE

AF:

0.00232

Gnomad OTH

AF:

0.0196

GnomAD4 exome

AF:

0.00600

AC:

6254

AN:

1043198

Hom.:

AF XY:

0.00558

AC XY:

2951

AN XY:

528720

show subpopulations

Gnomad4 AFR exome

AF:

0.0695

Gnomad4 AMR exome

AF:

0.00949

Gnomad4 ASJ exome

AF:

0.00347

Gnomad4 EAS exome

AF:

0.00146

Gnomad4 SAS exome

AF:

0.00360

Gnomad4 FIN exome

AF:

0.00637

Gnomad4 NFE exome

AF:

0.00427

Gnomad4 OTH exome

AF:

0.00749

GnomAD4 genome

AF:

0.0195

AC:

2676

AN:

137218

Hom.:

Cov.:

AF XY:

0.0186

AC XY:

1240

AN XY:

66750

show subpopulations

Gnomad4 AFR

AF:

0.0670

Gnomad4 AMR

AF:

0.00741

Gnomad4 ASJ

AF:

0.00203

Gnomad4 EAS

AF:

0.00145

Gnomad4 SAS

AF:

0.00212

Gnomad4 FIN

AF:

0.000962

Gnomad4 NFE

AF:

0.00232

Gnomad4 OTH

AF:

0.0194

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 11, 2023	- -

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

- -

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