6-131847856-GGTGTGTGTGTGTGTGTGTGTGTGTGT-GGTGTGTGTGTGTGTGTGTGTGTGTGTGT

Variant summary

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

The NM_006208.3(ENPP1):​c.313+45_313+46dupGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.20 ( 2793 hom., cov: 0)
Exomes 𝑓: 0.12 ( 194 hom. )

Consequence

ENPP1
NM_006208.3 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:5

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6
Variant 6-131847856-G-GGT is Benign according to our data. Variant chr6-131847856-G-GGT is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 355328.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=3}.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ENPP1NM_006208.3 linkc.313+45_313+46dupGT 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+8_313+9insGT intron_variant NM_006208.3 ENSP00000498074.1 P22413
ENPP1ENST00000486853.1 linkn.333+8_333+9insGT intron_variant 2
ENPP1ENST00000513998.5 linkn.313+8_313+9insGT intron_variant 5 ENSP00000422424.1 E9PE72
ENPP1ENST00000650507.1 linkn.*149+8_*149+9insGT intron_variant ENSP00000497375.1 A0A3B3IST7

Frequencies

GnomAD3 genomes
AF:
0.201
AC:
27476
AN:
136968
Hom.:
2795
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0964
Gnomad AMI
AF:
0.150
Gnomad AMR
AF:
0.262
Gnomad ASJ
AF:
0.242
Gnomad EAS
AF:
0.324
Gnomad SAS
AF:
0.234
Gnomad FIN
AF:
0.212
Gnomad MID
AF:
0.211
Gnomad NFE
AF:
0.230
Gnomad OTH
AF:
0.214
GnomAD4 exome
AF:
0.116
AC:
120008
AN:
1030852
Hom.:
194
Cov.:
14
AF XY:
0.122
AC XY:
63581
AN XY:
522134
show subpopulations
Gnomad4 AFR exome
AF:
0.0541
Gnomad4 AMR exome
AF:
0.170
Gnomad4 ASJ exome
AF:
0.168
Gnomad4 EAS exome
AF:
0.226
Gnomad4 SAS exome
AF:
0.154
Gnomad4 FIN exome
AF:
0.162
Gnomad4 NFE exome
AF:
0.102
Gnomad4 OTH exome
AF:
0.134
GnomAD4 genome
AF:
0.200
AC:
27479
AN:
137056
Hom.:
2793
Cov.:
0
AF XY:
0.204
AC XY:
13633
AN XY:
66670
show subpopulations
Gnomad4 AFR
AF:
0.0963
Gnomad4 AMR
AF:
0.262
Gnomad4 ASJ
AF:
0.242
Gnomad4 EAS
AF:
0.323
Gnomad4 SAS
AF:
0.235
Gnomad4 FIN
AF:
0.212
Gnomad4 NFE
AF:
0.230
Gnomad4 OTH
AF:
0.215

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:5
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Benign:4
Benign, criteria provided, single submitterclinical testingGeneDxOct 09, 2019- -
Likely benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 24, 2024- -
Likely benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
Hypophosphatemic Rickets, Recessive Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Arterial calcification, generalized, of infancy, 1 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingAl Jalila Children’s Genomics Center, Al Jalila Childrens Speciality HospitalJul 19, 2020- -

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.

Other links and lift over

dbSNP: rs59956343; hg19: chr6-132168996; API