3-40411941-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001248.4(ENTPD3):​c.416C>G​(p.Thr139Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. T139M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

ENTPD3
NM_001248.4 missense

Scores

12
5
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.21
Variant links:
Genes affected
ENTPD3 (HGNC:3365): (ectonucleoside triphosphate diphosphohydrolase 3) This gene encodes a plasma membrane-bound divalent cation-dependent E-type nucleotidase. The encoded protein is involved in the regulation of extracellular levels of ATP by hydrolysis of it and other nucleotides. Multiple transcript variants have been described. [provided by RefSeq, May 2014]
ENTPD3-AS1 (HGNC:26710): (ENTPD3 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.97

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ENTPD3NM_001248.4 linkc.416C>G p.Thr139Arg missense_variant Exon 5 of 11 ENST00000301825.8 NP_001239.2 O75355-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ENTPD3ENST00000301825.8 linkc.416C>G p.Thr139Arg missense_variant Exon 5 of 11 1 NM_001248.4 ENSP00000301825.3 O75355-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1458724
Hom.:
0
Cov.:
31
AF XY:
0.00000276
AC XY:
2
AN XY:
725504
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.91
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.18
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Benign
0.41
T;T;.
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.92
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.89
.;D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.97
D;D;D
MetaSVM
Uncertain
-0.13
T
MutationAssessor
Pathogenic
3.6
H;H;H
PrimateAI
Uncertain
0.61
T
PROVEAN
Pathogenic
-5.9
D;D;D
REVEL
Pathogenic
0.66
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.98
MutPred
0.84
Gain of MoRF binding (P = 0.0037);Gain of MoRF binding (P = 0.0037);Gain of MoRF binding (P = 0.0037);
MVP
0.78
MPC
0.39
ClinPred
1.0
D
GERP RS
5.6
Varity_R
0.94
gMVP
0.96

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.39
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.39
Position offset: 21

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: rs377644776; hg19: chr3-40453432; API