Genetic Variant NM_020354.5:c.77G>A (chr10-99661514-G-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_020354.5(ENTPD7):c.77G>A(p.Arg26His) variant causes a missense change. The variant allele was found at a frequency of 0.0000768 in 1,613,760 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R26C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

ENTPD7
NM_020354.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.47

Publications

0 publications found

Variant links:

Genes affected

ENTPD7 (HGNC:19745): (ectonucleoside triphosphate diphosphohydrolase 7) This gene encodes a purine-converting ectoenzyme which belongs to the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) family. The encoded protein hydrolyzes extracellular nucleoside triphosphates (UTP, GTP, and CTP) to nucleoside monophosphates as part of a purinergic signaling pathway. It contains two transmembrane domains at the N- and C-termini and a large, hydrophobic catalytic domain located in between. This gene affects oxidative stress as well as DNA damage and is a mediator of senescence. [provided by RefSeq, Mar 2017]

ENTPD7 links:

ENSG00000285932 (HGNC:):

ENSG00000285932 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30652353).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020354.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENTPD7	NM_020354.5	MANE Select	c.77G>A	p.Arg26His	missense	Exon 3 of 13	NP_065087.1	Q9NQZ7
ENTPD7	NM_001349962.2		c.83G>A	p.Arg28His	missense	Exon 4 of 14	NP_001336891.1
ENTPD7	NM_001349963.2		c.77G>A	p.Arg26His	missense	Exon 3 of 13	NP_001336892.1	Q9NQZ7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENTPD7	ENST00000370489.5	TSL:1 MANE Select	c.77G>A	p.Arg26His	missense	Exon 3 of 13	ENSP00000359520.4	Q9NQZ7
ENSG00000285932	ENST00000649102.1		n.*654-7609C>T		intron	N/A	ENSP00000497114.1	A0A3B3IRX1
ENTPD7	ENST00000902361.1		c.77G>A	p.Arg26His	missense	Exon 2 of 12	ENSP00000572420.1

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000167

AC:

AN:

251128

AF XY:

0.000162

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000636

AC:

AN:

1461614

Hom.:

Cov.:

AF XY:

0.0000811

AC XY:

AN XY:

727106

show subpopulations

African (AFR)

AF:

0.000299

AC:

AN:

33466

American (AMR)

AF:

0.000157

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.000510

AC:

AN:

86202

European-Finnish (FIN)

AF:

0.0000749

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

1111912

Other (OTH)

AF:

0.000116

AC:

AN:

60374

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

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000204

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.000650

AC:

AN:

41514

American (AMR)

AF:

0.0000655

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68000

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.000181

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000157

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.045

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0078

MetaRNN

Benign

0.31

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

5.5

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.29

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.013

Polyphen

1.0

Vest4

0.67

MVP

0.27

MPC

0.65

ClinPred

0.069

GERP RS

5.7

Varity_R

0.20

gMVP

0.57

Mutation Taster

=68/32

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over