rs570420189

Variant summary

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

The NM_004901.5(ENTPD4):​c.1825G>T​(p.Ala609Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000087 in 1,608,592 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. A609T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 1 hom. )

Consequence

ENTPD4
NM_004901.5 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08
Variant links:
Genes affected
ENTPD4 (HGNC:14573): (ectonucleoside triphosphate diphosphohydrolase 4) This gene encodes a member of the apyrase protein family. Apyrases are enzymes that catalyze the hydrolysis of nucleotide diphosphates and triphosphates in a calcium or magnesium-dependent manner. The encoded protein is an endo-apyrase and may play a role in salvaging nucleotides from lysosomes. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and these isoforms may differ in divalent cation dependence and substrate specificity. [provided by RefSeq, Sep 2011]

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=0.016626954).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ENTPD4NM_004901.5 linkc.1825G>T p.Ala609Ser missense_variant Exon 13 of 13 ENST00000358689.9 NP_004892.1 Q9Y227-1
ENTPD4NM_001128930.3 linkc.1801G>T p.Ala601Ser missense_variant Exon 13 of 13 NP_001122402.1 Q9Y227-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ENTPD4ENST00000358689.9 linkc.1825G>T p.Ala609Ser missense_variant Exon 13 of 13 1 NM_004901.5 ENSP00000351520.4 Q9Y227-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152204
Hom.:
0
Cov.:
32
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
GnomAD4 exome
AF:
0.00000893
AC:
13
AN:
1456388
Hom.:
1
Cov.:
31
AF XY:
0.00000552
AC XY:
4
AN XY:
724124
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:
0.0000234
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000901
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152204
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.00
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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.066
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.0010
DANN
Benign
0.69
DEOGEN2
Benign
0.030
T;.
Eigen
Benign
-2.5
Eigen_PC
Benign
-2.5
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.59
T;T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.017
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-2.0
N;.
PrimateAI
Benign
0.25
T
PROVEAN
Benign
0.29
N;N
REVEL
Benign
0.034
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0
B;B
Vest4
0.053
MutPred
0.10
Gain of glycosylation at A609 (P = 0.0375);.;
MVP
0.18
MPC
0.086
ClinPred
0.033
T
GERP RS
-11
Varity_R
0.018
gMVP
0.46

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: rs570420189; hg19: chr8-23290465; API