ENST00000453258.6:c.37+43773G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The ENST00000453258.6(ENTPD1):c.37+43773G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00603 in 1,536,624 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0048 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0062 ( 34 hom. )

Consequence

ENTPD1
ENST00000453258.6 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 1.33

Publications

5 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003439933).

BP6

Variant 10-95755766-G-A is Benign according to our data. Variant chr10-95755766-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 547899.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00481 (732/152272) while in subpopulation NFE AF = 0.00482 (328/68028). AF 95% confidence interval is 0.00439. There are 3 homozygotes in GnomAd4. There are 434 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
ENTPD1	NM_001164178.1 link	c.52G>A	p.Glu18Lys	missense_variant, splice_region_variant	Exon 1 of 10	NP_001157650.1	P49961-6
ENTPD1	NM_001440935.1 link	c.52G>A	p.Glu18Lys	missense_variant, splice_region_variant	Exon 1 of 9	NP_001427864.1
ENTPD1	NM_001320916.1 link	c.52G>A	p.Glu18Lys	missense_variant, splice_region_variant	Exon 1 of 10	NP_001307845.1	P49961

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
ENTPD1	ENST00000453258.6 link	c.37+43773G>A		intron_variant	Intron 1 of 9	1	ENSP00000390955.2	P49961-2
ENTPD1	ENST00000371207.8 link	c.52G>A	p.Glu18Lys	missense_variant, splice_region_variant	Exon 1 of 10	2	ENSP00000360250.3	P49961-6
ENTPD1	ENST00000543964.6 link	c.-181G>A		splice_region_variant	Exon 1 of 9	2	ENSP00000442968.1	P49961-5

Frequencies

GnomAD3 genomes

AF:

0.00482

AC:

733

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0306

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00482

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00335

AC:

475

AN:

141932

AF XY:

0.00333

show subpopulations

Gnomad AFR exome

AF:

0.000921

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0235

Gnomad NFE exome

AF:

0.00494

Gnomad OTH exome

AF:

0.00379

GnomAD4 exome

AF:

0.00616

AC:

8528

AN:

1384352

Hom.:

Cov.:

AF XY:

0.00601

AC XY:

4106

AN XY:

683206

show subpopulations

African (AFR)

AF:

0.000918

AC:

AN:

31580

American (AMR)

AF:

0.00120

AC:

AN:

35698

Ashkenazi Jewish (ASJ)

AF:

0.0000794

AC:

AN:

25178

East Asian (EAS)

AF:

0.00

AC:

AN:

35730

South Asian (SAS)

AF:

0.000303

AC:

AN:

79220

European-Finnish (FIN)

AF:

0.0209

AC:

733

AN:

34998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.00682

AC:

7350

AN:

1078360

Other (OTH)

AF:

0.00599

AC:

347

AN:

57892

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

381

762

1143

1524

1905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

296

592

888

1184

1480

<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:

0.00481

AC:

732

AN:

152272

Hom.:

Cov.:

AF XY:

0.00583

AC XY:

434

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

41556

American (AMR)

AF:

0.00196

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0306

AC:

324

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00482

AC:

328

AN:

68028

Other (OTH)

AF:

0.00190

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

109

145

181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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:

0.00370

Hom.:

Bravo

AF:

0.00270

TwinsUK

AF:

0.00998

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00409

AC:

ExAC

AF:

0.00114

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ENTPD1: PP3, BS2; ENTPD1-AS1: BS2 -

Sep 12, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary spastic paraplegia 64

Uncertain:1

Dec 29, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.42

M_CAP

Benign

0.0067

MetaRNN

Benign

0.0034

MetaSVM

Benign

-1.0

PhyloP100

1.3

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.73

REVEL

Benign

0.031

Sift

Benign

0.072

Sift4G

Benign

0.094

Vest4

0.20

MVP

0.13

MPC

0.18

ClinPred

0.0058

GERP RS

3.0

PromoterAI

-0.18

Neutral

(source)

gMVP

0.36

Mutation Taster

=267/33

polymorphism

(source)

Splicing

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