chr9-137435226-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001033113.2(ENTPD8):​c.1274C>T​(p.Pro425Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,611,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P425R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ENTPD8
NM_001033113.2 missense

Scores

1
1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.203

Publications

1 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.081251085).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ENTPD8NM_001033113.2 linkc.1274C>T p.Pro425Leu missense_variant Exon 9 of 10 ENST00000371506.7 NP_001028285.1 Q5MY95-1
ENTPD8NM_198585.3 linkc.1163C>T p.Pro388Leu missense_variant Exon 8 of 9 NP_940987.2 Q5MY95-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ENTPD8ENST00000371506.7 linkc.1274C>T p.Pro425Leu missense_variant Exon 9 of 10 5 NM_001033113.2 ENSP00000360561.2 Q5MY95-1
ENTPD8ENST00000344119.6 linkc.1163C>T p.Pro388Leu missense_variant Exon 8 of 9 1 ENSP00000344089.2 Q5MY95-2
ENTPD8ENST00000461823.1 linkn.2072C>T non_coding_transcript_exon_variant Exon 7 of 8 2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152252
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
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
GnomAD2 exomes
AF:
0.00000403
AC:
1
AN:
248134
AF XY:
0.00000741
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1459594
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
726176
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33474
American (AMR)
AF:
0.00
AC:
0
AN:
44698
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26112
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39690
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86240
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51486
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
0.00000540
AC:
6
AN:
1111768
Other (OTH)
AF:
0.00
AC:
0
AN:
60364
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.450
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00000657
AC:
1
AN:
152252
Hom.:
0
Cov.:
34
AF XY:
0.0000134
AC XY:
1
AN XY:
74380
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41468
American (AMR)
AF:
0.00
AC:
0
AN:
15292
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5200
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4838
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68036
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000712
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.093
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
16
DANN
Benign
0.95
DEOGEN2
Benign
0.18
.;T;T
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.52
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.69
T;T;.
M_CAP
Benign
0.0049
T
MetaRNN
Benign
0.081
T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.0
.;M;M
PhyloP100
-0.20
PrimateAI
Benign
0.31
T
PROVEAN
Pathogenic
-4.4
D;D;D
REVEL
Benign
0.030
Sift
Benign
0.23
T;T;T
Sift4G
Benign
0.29
T;T;T
Polyphen
0.024
B;B;B
Vest4
0.28
MutPred
0.51
.;Loss of disorder (P = 0.0301);Loss of disorder (P = 0.0301);
MVP
0.081
MPC
0.066
ClinPred
0.090
T
GERP RS
3.4
Varity_R
0.11
gMVP
0.40
Mutation Taster
=91/9
polymorphism

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

Other links and lift over

dbSNP: rs1409650051; hg19: chr9-140329678; API