rs3793744

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001776.6(ENTPD1):c.877G>A(p.Val293Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00343 in 1,614,134 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V293V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.017 ( 78 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 67 hom. )

Consequence

ENTPD1
NM_001776.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.254

Publications

9 publications found

Variant links:

Genes affected

ENTPD1 (HGNC:3363): (ectonucleoside triphosphate diphosphohydrolase 1) The protein encoded by this gene is a plasma membrane protein that hydrolyzes extracellular ATP and ADP to AMP. Inhibition of this protein's activity may confer anticancer benefits. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

ENTPD1 links:

ENTPD1-AS1 (HGNC:45203): (ENTPD1 antisense RNA 1)

ENTPD1-AS1 links:

ENSG00000240527 (HGNC:):

ENSG00000240527 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022000968).

BP6

Variant 10-95847509-G-A is Benign according to our data. Variant chr10-95847509-G-A is described in ClinVar as Benign. ClinVar VariationId is 703843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTPD1	NM_001776.6 link	c.877G>A	p.Val293Ile	missense_variant	Exon 7 of 10	ENST00000371205.5	NP_001767.3	P49961-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENTPD1	ENST00000371205.5 link	c.877G>A	p.Val293Ile	missense_variant	Exon 7 of 10	1	NM_001776.6	ENSP00000360248.4		P49961-1

Frequencies

GnomAD3 genomes

AF:

0.0170

AC:

2594

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0573

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00628

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0148

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0158

GnomAD2 exomes

AF:

0.00548

AC:

1379

AN:

251430

AF XY:

0.00406

show subpopulations

Gnomad AFR exome

AF:

0.0581

Gnomad AMR exome

AF:

0.00266

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.0158

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000211

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00200

AC:

2917

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

1260

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.0566

AC:

1896

AN:

33480

American (AMR)

AF:

0.00291

AC:

130

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000574

AC:

AN:

26132

East Asian (EAS)

AF:

0.0111

AC:

442

AN:

39698

South Asian (SAS)

AF:

0.000162

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000104

AC:

116

AN:

1111996

Other (OTH)

AF:

0.00470

AC:

284

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

181

363

544

726

907

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0172

AC:

2615

AN:

152268

Hom.:

Cov.:

AF XY:

0.0168

AC XY:

1251

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0576

AC:

2392

AN:

41534

American (AMR)

AF:

0.00627

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.0149

AC:

AN:

5180

South Asian (SAS)

AF:

0.000830

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68028

Other (OTH)

AF:

0.0161

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

122

244

366

488

610

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00827

Hom.:

Bravo

AF:

0.0192

ESP6500AA

AF:

0.0601

AC:

265

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.00631

AC:

766

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ENTPD1-related disorder

Benign:1

Jan 03, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Hereditary spastic paraplegia

Benign:1

Jan 17, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary spastic paraplegia 64

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.029

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.080

.;.;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.55

T;T;T;T

MetaRNN

Benign

0.0022

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.43

.;.;.;N

PhyloP100

-0.25

PrimateAI

Benign

0.22

PROVEAN

Benign

0.070

N;N;N;N

REVEL

Benign

0.019

Sift

Benign

0.50

T;T;T;T

Sift4G

Benign

0.52

T;T;T;T

Polyphen

0.0040

B;.;.;B

Vest4

0.030

MVP

0.082

MPC

0.13

ClinPred

0.00030

GERP RS

-5.7

Varity_R

0.019

gMVP

0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over