Variant 20-25222961-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_001247.5(ENTPD6):c.1169C>T(p.Ala390Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000335 in 1,494,440 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 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

ENTPD6
NM_001247.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.92

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:

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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=0.148058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENTPD6	NM_001247.5 linkuse as main transcript	c.1169C>T	p.Ala390Val	missense_variant	12/15	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.1169C>T	p.Ala390Val	missense_variant	12/15	1	NM_001247.5	ENSP00000365840	P4	O75354-1

Frequencies

GnomAD3 genomes

AF:

0.00000672

AC:

AN:

148782

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000297

AC:

AN:

1345658

Hom.:

Cov.:

AF XY:

0.00000449

AC XY:

AN XY:

668734

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000385

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000672

AC:

AN:

148782

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72538

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000149

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Jun 13, 2023

The c.1169C>T (p.A390V) alteration is located in exon 12 (coding exon 11) of the ENTPD6 gene. This alteration results from a C to T substitution at nucleotide position 1169, causing the alanine (A) at amino acid position 390 to be replaced by a valine (V). 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

0.10

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.0033

.;.;T;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.070

FATHMM_MKL

Benign

0.67

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.0068

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.095

.;.;N;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.080

N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.86

T;T;T;T

Sift4G

Benign

0.74

T;T;T;T

Polyphen

0.0070

B;.;B;B

Vest4

0.20

MutPred

0.63

.;.;Gain of sheet (P = 0.0827);.;

MVP

0.26

MPC

0.26

ClinPred

0.69

GERP RS

5.5

Varity_R

0.049

gMVP

0.43

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