chr9-137435301-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001033113.2(ENTPD8):​c.1199G>A​(p.Arg400Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,612,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ENTPD8
NM_001033113.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.02
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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03437051).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ENTPD8NM_001033113.2 linkuse as main transcriptc.1199G>A p.Arg400Gln missense_variant 9/10 ENST00000371506.7 NP_001028285.1
ENTPD8NM_198585.3 linkuse as main transcriptc.1088G>A p.Arg363Gln missense_variant 8/9 NP_940987.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ENTPD8ENST00000371506.7 linkuse as main transcriptc.1199G>A p.Arg400Gln missense_variant 9/105 NM_001033113.2 ENSP00000360561 P1Q5MY95-1
ENTPD8ENST00000344119.6 linkuse as main transcriptc.1088G>A p.Arg363Gln missense_variant 8/91 ENSP00000344089 Q5MY95-2
ENTPD8ENST00000461823.1 linkuse as main transcriptn.1997G>A non_coding_transcript_exon_variant 7/82

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152234
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000241
AC:
6
AN:
248490
Hom.:
0
AF XY:
0.0000296
AC XY:
4
AN XY:
135000
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000870
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000179
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000185
AC:
27
AN:
1459962
Hom.:
0
Cov.:
33
AF XY:
0.0000179
AC XY:
13
AN XY:
726292
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000895
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152352
Hom.:
0
Cov.:
34
AF XY:
0.0000403
AC XY:
3
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 08, 2024The c.1199G>A (p.R400Q) alteration is located in exon 9 (coding exon 8) of the ENTPD8 gene. This alteration results from a G to A substitution at nucleotide position 1199, causing the arginine (R) at amino acid position 400 to be replaced by a glutamine (Q). 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
0.10
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
10
DANN
Benign
0.96
DEOGEN2
Benign
0.019
.;T;T
Eigen
Benign
-0.92
Eigen_PC
Benign
-0.96
FATHMM_MKL
Benign
0.053
N
LIST_S2
Benign
0.55
T;T;.
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.034
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
.;L;L
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.39
N;N;N
REVEL
Benign
0.0060
Sift
Benign
0.32
T;T;T
Sift4G
Benign
0.67
T;T;T
Polyphen
0.48
P;B;B
Vest4
0.14
MVP
0.014
MPC
0.072
ClinPred
0.12
T
GERP RS
0.77
Varity_R
0.047
gMVP
0.30

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: rs78674871; hg19: chr9-140329753; API