3-40416033-G-A

Variant names:

• chr3-40416033-G-A
• rs34266806
• NM_001248.4:c.791G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001248.4(ENTPD3):​c.791G>A​(p.Arg264Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00492 in 1,613,954 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (33 hom.)
• Consequence: ENTPD3 NM_001248.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.92
• Publications: 14 publications found

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:):

ENTPD3-AS1 (HGNC:26710): (ENTPD3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01149714).
• BP6: Variant 3-40416033-G-A is Benign according to our data. Variant chr3-40416033-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2653692.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001248.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD3	NM_001248.4	MANE Select	c.791G>A	p.Arg264Gln	missense	Exon 7 of 11	NP_001239.2	O75355-1
	ENTPD3	NM_001291960.2		c.791G>A	p.Arg264Gln	missense	Exon 7 of 11	NP_001278889.1	O75355-1
	ENTPD3	NM_001291961.2		c.791G>A	p.Arg264Gln	missense	Exon 7 of 11	NP_001278890.1	O75355-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD3	ENST00000301825.8	TSL:1 MANE Select	c.791G>A	p.Arg264Gln	missense	Exon 7 of 11	ENSP00000301825.3	O75355-1
	ENTPD3	ENST00000456402.5	TSL:1	c.791G>A	p.Arg264Gln	missense	Exon 7 of 11	ENSP00000401565.1	O75355-1
	ENTPD3	ENST00000445129.1	TSL:1	c.791G>A	p.Arg264Gln	missense	Exon 6 of 10	ENSP00000404671.1	O75355-2

Frequencies

GnomAD3 genomes AF: 0.00384 AC: 584 AN: 152122 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000942

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00415

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00612

Gnomad OTH AF: 0.00768

GnomAD2 exomes AF: 0.00348 AC: 873 AN: 250774 AF XY: 0.00351

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00359

Gnomad ASJ exome AF: 0.000398

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00393

Gnomad NFE exome AF: 0.00542

Gnomad OTH exome AF: 0.00442

GnomAD4 exome AF: 0.00503 AC: 7351 AN: 1461714 Hom.: 33 Cov.: 31 AF XY: 0.00490 AC XY: 3564 AN XY: 727146

African (AFR) AF: 0.000747 AC: 25 AN: 33470

American (AMR) AF: 0.00382 AC: 171 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.000612 AC: 16 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86238

European-Finnish (FIN) AF: 0.00472 AC: 252 AN: 53410

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5764

European-Non Finnish (NFE) AF: 0.00596 AC: 6625 AN: 1111918

Other (OTH) AF: 0.00414 AC: 250 AN: 60386

GnomAD4 genome AF: 0.00384 AC: 584 AN: 152240 Hom.: 4 Cov.: 32 AF XY: 0.00360 AC XY: 268 AN XY: 74444

African (AFR) AF: 0.000939 AC: 39 AN: 41536

American (AMR) AF: 0.00431 AC: 66 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00415 AC: 44 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00612 AC: 416 AN: 68016

Other (OTH) AF: 0.00760 AC: 16 AN: 2106

Alfa AF: 0.00473 Hom.: 5

Bravo AF: 0.00396

TwinsUK AF: 0.00701 AC: 26

ALSPAC AF: 0.00675 AC: 26

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.00663 AC: 57

ExAC AF: 0.00344 AC: 418

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00638

EpiControl AF: 0.00581

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.022
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		2.9
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.052
Sift	Benign	0.25	T
Sift4G	Benign	0.38	T
Polyphen		0.31	B
Vest4		0.40
MVP		0.32
MPC		0.088
ClinPred		0.023	T
GERP RS		3.5
Varity_R		0.15
gMVP		0.50
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34266806; hg19: chr3-40457524; COSMIC: COSV57194592;