Variant chr9-137436014-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001033113.2(ENTPD8):c.1049A>G(p.Tyr350Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,360 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ENTPD8
NM_001033113.2 missense, splice_region

Scores

Splicing: ADA: 0.8725

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.883

Variant links:

Genes affected

ENTPD8 (HGNC:24860): (ectonucleoside triphosphate diphosphohydrolase 8) Predicted to enable guanosine-diphosphatase activity and uridine-diphosphatase activity. Predicted to be involved in nucleoside diphosphate catabolic process. Predicted to act upstream of or within nucleoside diphosphate biosynthetic process and nucleoside monophosphate biosynthetic process. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENTPD8 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENTPD8	NM_001033113.2 linkuse as main transcript	c.1049A>G	p.Tyr350Cys	missense_variant, splice_region_variant	7/10	ENST00000371506.7	NP_001028285.1
ENTPD8	NM_198585.3 linkuse as main transcript	c.1049A>G	p.Tyr350Cys	missense_variant, splice_region_variant	7/9		NP_940987.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENTPD8	ENST00000371506.7 linkuse as main transcript	c.1049A>G	p.Tyr350Cys	missense_variant, splice_region_variant	7/10	5	NM_001033113.2	ENSP00000360561	P1	Q5MY95-1
ENTPD8	ENST00000344119.6 linkuse as main transcript	c.1049A>G	p.Tyr350Cys	missense_variant, splice_region_variant	7/9	1		ENSP00000344089		Q5MY95-2
ENTPD8	ENST00000461823.1 linkuse as main transcript	n.1847A>G		splice_region_variant, non_coding_transcript_exon_variant	5/8	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460360

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726474

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

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

Oct 05, 2023

The c.1049A>G (p.Y350C) alteration is located in exon 7 (coding exon 6) of the ENTPD8 gene. This alteration results from a A to G substitution at nucleotide position 1049, causing the tyrosine (Y) at amino acid position 350 to be replaced by a cysteine (C). 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

0.27

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

.;T;T

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.077

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.51

T;D;.

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.57

D;D;D

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.8

M;M;M

MutationTaster

Benign

0.77

D;D;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-2.0

N;D;D

REVEL

Benign

0.21

Sift

Benign

0.14

T;T;T

Sift4G

Uncertain

0.038

D;T;T

Polyphen

1.0

D;D;D

Vest4

0.55

MVP

0.14

MPC

0.16

ClinPred

0.28

GERP RS

3.1

Varity_R

0.67

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.87

dbscSNV1_RF

Benign

0.62

SpliceAI score (max)

0.33

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.33

Position offset: 1

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