Variant 20-25207251-C-G 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.230C>G(p.Ala77Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ENTPD6
NM_001247.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.126

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=0.07229394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENTPD6	NM_001247.5 linkuse as main transcript	c.230C>G	p.Ala77Gly	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.230C>G	p.Ala77Gly	missense_variant	3/15	1	NM_001247.5	ENSP00000365840	P4	O75354-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461706

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727164

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

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

Mar 25, 2024

The c.230C>G (p.A77G) alteration is located in exon 3 (coding exon 2) of the ENTPD6 gene. This alteration results from a C to G substitution at nucleotide position 230, causing the alanine (A) at amino acid position 77 to be replaced by a glycine (G). 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

0.078

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.16

DANN

Benign

0.69

DEOGEN2

Benign

0.012

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

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.78

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

M_CAP

Benign

0.0039

MetaRNN

Benign

0.072

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

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

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.3

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

REVEL

Benign

0.044

Sift

Benign

0.31

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

Sift4G

Benign

0.37

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

Polyphen

0.0010

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

Vest4

0.12

MutPred

0.34

.;.;Gain of methylation at R76 (P = 0.0626);.;.;Gain of methylation at R76 (P = 0.0626);.;.;Gain of methylation at R76 (P = 0.0626);

MVP

0.12

MPC

0.25

ClinPred

0.24

GERP RS

-7.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.029

gMVP

0.49

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