Variant 3-40416000-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001248.4(ENTPD3):c.758C>T(p.Thr253Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00007 in 1,613,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

ENTPD3
NM_001248.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.223

Variant links:

Genes affected

ENTPD3 (HGNC:3365): (ectonucleoside triphosphate diphosphohydrolase 3) This gene encodes a plasma membrane-bound divalent cation-dependent E-type nucleotidase. The encoded protein is involved in the regulation of extracellular levels of ATP by hydrolysis of it and other nucleotides. Multiple transcript variants have been described. [provided by RefSeq, May 2014]

ENTPD3 links:

ENTPD3-AS1 (HGNC:):

ENTPD3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23580185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENTPD3	NM_001248.4 linkuse as main transcript	c.758C>T	p.Thr253Met	missense_variant	7/11	ENST00000301825.8	NP_001239.2	O75355-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENTPD3	ENST00000301825.8 linkuse as main transcript	c.758C>T	p.Thr253Met	missense_variant	7/11	1	NM_001248.4	ENSP00000301825.3		O75355-1

Frequencies

GnomAD3 genomes

AF:

0.0000462

AC:

AN:

151420

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000590

Gnomad OTH

AF:

0.000483

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

250952

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

135586

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000883

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000725

AC:

106

AN:

1461794

Hom.:

Cov.:

AF XY:

0.0000880

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.0000863

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000462

AC:

AN:

151420

Hom.:

Cov.:

AF XY:

0.0000406

AC XY:

AN XY:

73942

show subpopulations

Gnomad4 AFR

AF:

0.0000486

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000590

Gnomad4 OTH

AF:

0.000483

Alfa

AF:

0.000106

Hom.:

Bravo

AF:

0.0000604

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2023

The c.758C>T (p.T253M) alteration is located in exon 7 (coding exon 6) of the ENTPD3 gene. This alteration results from a C to T substitution at nucleotide position 758, causing the threonine (T) at amino acid position 253 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.74

.;T;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;M;M

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.11

Sift

Uncertain

0.0060

D;D;D

Sift4G

Benign

0.062

T;T;D

Polyphen

0.99

D;D;.

Vest4

0.40

MVP

0.24

MPC

0.077

ClinPred

0.21

GERP RS

2.3

Varity_R

0.11

gMVP

0.55

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

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