Genetic Variant ENTPD8:p.Glu422Asp (chr9-137435234-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001033113.2(ENTPD8):c.1266G>C(p.Glu422Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ENTPD8
NM_001033113.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.84

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049585164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTPD8	NM_001033113.2 link	c.1266G>C	p.Glu422Asp	missense_variant	Exon 9 of 10	ENST00000371506.7	NP_001028285.1	Q5MY95-1
ENTPD8	NM_198585.3 link	c.1155G>C	p.Glu385Asp	missense_variant	Exon 8 of 9		NP_940987.2	Q5MY95-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENTPD8	ENST00000371506.7 link	c.1266G>C	p.Glu422Asp	missense_variant	Exon 9 of 10	5	NM_001033113.2	ENSP00000360561.2	Q5MY95-1
ENTPD8	ENST00000344119.6 link	c.1155G>C	p.Glu385Asp	missense_variant	Exon 8 of 9	1		ENSP00000344089.2	Q5MY95-2
ENTPD8	ENST00000461823.1 link	n.2064G>C		non_coding_transcript_exon_variant	Exon 7 of 8	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459790

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726244

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51634

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111808

Other (OTH)

AF:

0.00

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.4

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.021

.;T;T

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.56

T;T;.

M_CAP

Benign

0.0041

MetaRNN

Benign

0.050

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.2

.;L;L

PhyloP100

-1.8

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.0

N;N;N

REVEL

Benign

0.028

Sift

Benign

0.58

T;T;T

Sift4G

Benign

0.44

T;T;T

Polyphen

0.0030

B;B;B

Vest4

0.12

MutPred

0.30

.;Loss of disorder (P = 0.1002);Loss of disorder (P = 0.1002);

MVP

0.014

MPC

0.057

ClinPred

0.15

GERP RS

0.038

Varity_R

0.18

gMVP

0.28

Mutation Taster

=81/19

polymorphism

(source)

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

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9-137435234-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over