dbSNP rs181530826: ENTPD8:p.Thr358Ile (chr9-137435807-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001033113.2(ENTPD8):c.1073C>T(p.Thr358Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00059 in 1,613,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00061 ( 0 hom. )

Consequence

ENTPD8
NM_001033113.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.27

Publications

4 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.2174659).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTPD8	NM_001033113.2 link	c.1073C>T	p.Thr358Ile	missense_variant	Exon 8 of 10	ENST00000371506.7	NP_001028285.1	Q5MY95-1
ENTPD8	NM_198585.3 link	c.1050+206C>T		intron_variant	Intron 7 of 8		NP_940987.2	Q5MY95-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENTPD8	ENST00000371506.7 link	c.1073C>T	p.Thr358Ile	missense_variant	Exon 8 of 10	5	NM_001033113.2	ENSP00000360561.2	Q5MY95-1
ENTPD8	ENST00000344119.6 link	c.1050+206C>T		intron_variant	Intron 7 of 8	1		ENSP00000344089.2	Q5MY95-2
ENTPD8	ENST00000461823.1 link	n.1871C>T		non_coding_transcript_exon_variant	Exon 6 of 8	2

Frequencies

GnomAD3 genomes

AF:

0.000440

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000402

AC:

100

AN:

249020

AF XY:

0.000443

show subpopulations

Gnomad AFR exome

AF:

0.000195

Gnomad AMR exome

AF:

0.000348

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000612

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000606

AC:

885

AN:

1461246

Hom.:

Cov.:

AF XY:

0.000620

AC XY:

451

AN XY:

726964

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33478

American (AMR)

AF:

0.000335

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000673

AC:

AN:

86152

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53038

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000698

AC:

776

AN:

1111896

Other (OTH)

AF:

0.000513

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

136

182

227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000440

AC:

AN:

152358

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.0000240

AC:

AN:

41586

American (AMR)

AF:

0.000457

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000823

AC:

AN:

68030

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000568

Hom.:

Bravo

AF:

0.000450

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000706

AC:

ExAC

AF:

0.000429

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.000711

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 15, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1073C>T (p.T358I) alteration is located in exon 8 (coding exon 7) of the ENTPD8 gene. This alteration results from a C to T substitution at nucleotide position 1073, causing the threonine (T) at amino acid position 358 to be replaced by an isoleucine (I). 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

0.31

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.44

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.074

T;T

Eigen

Benign

0.14

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.78

T;.

M_CAP

Benign

0.028

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;M

PhyloP100

1.3

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.13

Sift

Uncertain

0.0050

D;D

Sift4G

Benign

0.086

T;T

Polyphen

0.77

P;P

Vest4

0.70

MVP

0.12

MPC

0.18

ClinPred

0.076

GERP RS

4.2

Varity_R

0.41

gMVP

0.82

Mutation Taster

=71/29

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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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rs181530826

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over