10-99685842-T-G

Variant summary

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

The NM_020354.5(ENTPD7):​c.599T>G​(p.Phe200Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,868 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F200S) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.000013 ( 0 hom. )

Consequence

ENTPD7
NM_020354.5 missense

Scores

6
9
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.45
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]

Genome browser will be placed here

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 rank MANE Protein UniProt
ENTPD7NM_020354.5 linkc.599T>G p.Phe200Cys missense_variant Exon 6 of 13 ENST00000370489.5 NP_065087.1 Q9NQZ7
ENTPD7NM_001349962.2 linkc.605T>G p.Phe202Cys missense_variant Exon 7 of 14 NP_001336891.1
ENTPD7NM_001349963.2 linkc.599T>G p.Phe200Cys missense_variant Exon 6 of 13 NP_001336892.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ENTPD7ENST00000370489.5 linkc.599T>G p.Phe200Cys missense_variant Exon 6 of 13 1 NM_020354.5 ENSP00000359520.4 Q9NQZ7
ENSG00000285932ENST00000649102.1 linkn.*539+5764A>C intron_variant Intron 9 of 12 ENSP00000497114.1 A0A3B3IRX1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152054
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000130
AC:
19
AN:
1461814
Hom.:
0
Cov.:
31
AF XY:
0.00000963
AC XY:
7
AN XY:
727218
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:
0.0000171
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152054
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74272
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.91
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.010
CADD
Pathogenic
29
DANN
Uncertain
0.98
DEOGEN2
Benign
0.079
T
Eigen
Pathogenic
0.78
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.96
D
M_CAP
Benign
0.027
D
MetaRNN
Uncertain
0.74
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.5
M
PrimateAI
Pathogenic
0.79
T
PROVEAN
Uncertain
-3.7
D
REVEL
Uncertain
0.36
Sift
Uncertain
0.0080
D
Sift4G
Uncertain
0.035
D
Polyphen
1.0
D
Vest4
0.80
MutPred
0.58
Loss of stability (P = 0.0618);
MVP
0.46
MPC
0.80
ClinPred
0.99
D
GERP RS
5.5
Varity_R
0.76
gMVP
0.85

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.

Other links and lift over

dbSNP: rs201287793; hg19: chr10-101445599; API