6-131847856-GGTGTGTGTGTGTGTGTGTGTGTGTGT-GGTGTGTGTGTGTGTGTGTGTGTGT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_006208.3(ENPP1):​c.313+45_313+46delGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,151,148 control chromosomes in the GnomAD database, including 1,863 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1306 hom., cov: 0)
Exomes 𝑓: 0.15 ( 557 hom. )

Consequence

ENPP1
NM_006208.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6
Variant 6-131847856-GGT-G is Benign according to our data. Variant chr6-131847856-GGT-G is described in ClinVar as [Benign]. Clinvar id is 355332.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-131847856-GGT-G is described in Lovd as [Likely_benign].
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ENPP1NM_006208.3 linkc.313+45_313+46delGT intron_variant ENST00000647893.1 NP_006199.2 P22413

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ENPP1ENST00000647893.1 linkc.313+9_313+10delGT intron_variant NM_006208.3 ENSP00000498074.1 P22413
ENPP1ENST00000486853.1 linkn.333+9_333+10delGT intron_variant 2
ENPP1ENST00000513998.5 linkn.313+9_313+10delGT intron_variant 5 ENSP00000422424.1 E9PE72
ENPP1ENST00000650507.1 linkn.*149+9_*149+10delGT intron_variant ENSP00000497375.1 A0A3B3IST7

Frequencies

GnomAD3 genomes
AF:
0.143
AC:
19621
AN:
136864
Hom.:
1307
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.108
Gnomad AMI
AF:
0.150
Gnomad AMR
AF:
0.141
Gnomad ASJ
AF:
0.113
Gnomad EAS
AF:
0.116
Gnomad SAS
AF:
0.196
Gnomad FIN
AF:
0.278
Gnomad MID
AF:
0.191
Gnomad NFE
AF:
0.144
Gnomad OTH
AF:
0.128
GnomAD4 exome
AF:
0.154
AC:
155702
AN:
1014198
Hom.:
557
AF XY:
0.160
AC XY:
81912
AN XY:
513220
show subpopulations
Gnomad4 AFR exome
AF:
0.122
Gnomad4 AMR exome
AF:
0.180
Gnomad4 ASJ exome
AF:
0.186
Gnomad4 EAS exome
AF:
0.221
Gnomad4 SAS exome
AF:
0.208
Gnomad4 FIN exome
AF:
0.265
Gnomad4 NFE exome
AF:
0.137
Gnomad4 OTH exome
AF:
0.171
GnomAD4 genome
AF:
0.143
AC:
19625
AN:
136950
Hom.:
1306
Cov.:
0
AF XY:
0.150
AC XY:
9982
AN XY:
66570
show subpopulations
Gnomad4 AFR
AF:
0.107
Gnomad4 AMR
AF:
0.141
Gnomad4 ASJ
AF:
0.113
Gnomad4 EAS
AF:
0.117
Gnomad4 SAS
AF:
0.197
Gnomad4 FIN
AF:
0.278
Gnomad4 NFE
AF:
0.144
Gnomad4 OTH
AF:
0.126

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxOct 20, 2019- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
Hypophosphatemic Rickets, Recessive Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Arterial calcification, generalized, of infancy, 1 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs59956343; hg19: chr6-132168996; API