Variant 20-25207220-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001247.5(ENTPD6):c.199G>A(p.Ala67Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000482 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00051 ( 0 hom. )

Consequence

ENTPD6
NM_001247.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31

Variant links:

Genes affected

ENTPD6 (HGNC:3368): (ectonucleoside triphosphate diphosphohydrolase 6) ENTPD6 is similar to E-type nucleotidases (NTPases). NTPases, such as CD39, mediate catabolism of extracellular nucleotides. ENTPD6 contains 4 apyrase-conserved regions which are characteristic of NTPases. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ENTPD6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03007859).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENTPD6	NM_001247.5 linkuse as main transcript	c.199G>A	p.Ala67Thr	missense_variant	3/15	ENST00000376652.9	NP_001238.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENTPD6	ENST00000376652.9 linkuse as main transcript	c.199G>A	p.Ala67Thr	missense_variant	3/15	1	NM_001247.5	ENSP00000365840	P4	O75354-1

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000485

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000300

AC:

AN:

249886

Hom.:

AF XY:

0.000229

AC XY:

AN XY:

135238

show subpopulations

Gnomad AFR exome

AF:

0.000185

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:

0.000623

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000506

AC:

739

AN:

1461774

Hom.:

Cov.:

AF XY:

0.000499

AC XY:

363

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000750

Gnomad4 NFE exome

AF:

0.000635

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000256

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000463

Hom.:

Bravo

AF:

0.000329

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000329

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000474

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

Apr 28, 2022

The c.199G>A (p.A67T) alteration is located in exon 3 (coding exon 2) of the ENTPD6 gene. This alteration results from a G to A substitution at nucleotide position 199, causing the alanine (A) at amino acid position 67 to be replaced by a threonine (T). 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

0.072

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0097

.;.;T;.;T;T;.;T;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.68

T;T;T;T;T;T;T;T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.030

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;.;L;.;.;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.87

N;N;N;N;N;N;N;N;N

REVEL

Benign

0.024

Sift

Benign

0.083

T;T;T;T;T;D;T;D;D

Sift4G

Benign

0.52

T;T;T;T;T;T;T;T;T

Polyphen

0.20

B;.;B;.;.;B;.;.;.

Vest4

0.27

MVP

0.18

MPC

0.25

ClinPred

0.020

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.037

gMVP

0.62

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