8-23432952-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_004901.5(ENTPD4):​c.1825G>A​(p.Ala609Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000528 in 1,608,708 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

ENTPD4
NM_004901.5 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

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 -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.011351913).
BP6
Variant 8-23432952-C-T is Benign according to our data. Variant chr8-23432952-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2275720.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ENTPD4NM_004901.5 linkc.1825G>A p.Ala609Thr missense_variant Exon 13 of 13 ENST00000358689.9 NP_004892.1 Q9Y227-1
ENTPD4NM_001128930.3 linkc.1801G>A p.Ala601Thr 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>A p.Ala609Thr missense_variant Exon 13 of 13 1 NM_004901.5 ENSP00000351520.4 Q9Y227-1

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152204
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000118
AC:
28
AN:
237040
Hom.:
0
AF XY:
0.000124
AC XY:
16
AN XY:
128752
show subpopulations
Gnomad AFR exome
AF:
0.0000672
Gnomad AMR exome
AF:
0.000509
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000948
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000474
AC:
69
AN:
1456386
Hom.:
0
Cov.:
31
AF XY:
0.0000442
AC XY:
32
AN XY:
724122
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000412
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000760
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000397
Gnomad4 OTH exome
AF:
0.0000499
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152322
Hom.:
0
Cov.:
32
AF XY:
0.0000940
AC XY:
7
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.000473
Bravo
AF:
0.0000869
ExAC
AF:
0.000124
AC:
15

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Sep 01, 2021
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.065
BayesDel_addAF
Benign
-0.62
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
0.019
DANN
Benign
0.85
DEOGEN2
Benign
0.033
T;.
Eigen
Benign
-2.2
Eigen_PC
Benign
-2.3
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.61
T;T
M_CAP
Benign
0.0022
T
MetaRNN
Benign
0.011
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;.
PrimateAI
Benign
0.25
T
PROVEAN
Benign
0.10
N;N
REVEL
Benign
0.027
Sift
Benign
0.35
T;T
Sift4G
Benign
0.50
T;T
Polyphen
0.039
B;B
Vest4
0.067
MVP
0.16
MPC
0.094
ClinPred
0.070
T
GERP RS
-11
Varity_R
0.016
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; COSMIC: COSV62269146; COSMIC: COSV62269146; API