Variant 10-95755766-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id is 547899.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}. Variant chr10-95755766-G-A is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENTPD1-AS1	NR_038444.1 linkuse as main transcript	n.1702C>T		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENTPD1-AS1	ENST00000669711.1 linkuse as main transcript	n.947C>T		non_coding_transcript_exon_variant	6/7

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

GnomAD3 exomes

AF:

0.00335

AC:

475

AN:

141932

Hom.:

AF XY:

0.00333

AC XY:

253

AN XY:

75902

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 SAS exome

AF:

0.000220

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

Gnomad4 AFR exome

AF:

0.000918

Gnomad4 AMR exome

AF:

0.00120

Gnomad4 ASJ exome

AF:

0.0000794

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000303

Gnomad4 FIN exome

AF:

0.0209

Gnomad4 NFE exome

AF:

0.00682

Gnomad4 OTH exome

AF:

0.00599

GnomAD4 genome

AF:

0.00481

AC:

732

AN:

152272

Hom.:

Cov.:

AF XY:

0.00583

AC XY:

434

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0306

Gnomad4 NFE

AF:

0.00482

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00381

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

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 12, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	ENTPD1: PP3, BS2; ENTPD1-AS1: BS2 -

Hereditary spastic paraplegia 64

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Dec 29, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

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

MutationTaster

Benign

1.0

D;N;N;N

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

gMVP

0.36

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