3-40392031-G-T

Variant names:

• chr3-40392031-G-T
• rs1302744571
• NM_001248.4:c.49G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001248.4(ENTPD3):​c.49G>T​(p.Ala17Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ENTPD3 NM_001248.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.804
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06619945).

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.49G>T	p.Ala17Ser	missense	Exon 3 of 11	NP_001239.2	O75355-1
	ENTPD3	NM_001291960.2		c.49G>T	p.Ala17Ser	missense	Exon 3 of 11	NP_001278889.1	O75355-1
	ENTPD3	NM_001291961.2		c.49G>T	p.Ala17Ser	missense	Exon 3 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.49G>T	p.Ala17Ser	missense	Exon 3 of 11	ENSP00000301825.3	O75355-1
	ENTPD3	ENST00000456402.5	TSL:1	c.49G>T	p.Ala17Ser	missense	Exon 3 of 11	ENSP00000401565.1	O75355-1
	ENTPD3	ENST00000445129.1	TSL:1	c.49G>T	p.Ala17Ser	missense	Exon 2 of 10	ENSP00000404671.1	O75355-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251456 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461840 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727218

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111998

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PhyloP100		0.80
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.016
Sift	Benign	0.30	T
Sift4G	Benign	0.66	T
Polyphen		0.44	B
Vest4		0.18
MutPred		0.25		Gain of relative solvent accessibility (P = 0.0023)
MVP		0.30
MPC		0.056
ClinPred		0.093	T
GERP RS		2.2
Varity_R		0.051
gMVP		0.34
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs1302744571; hg19: chr3-40433522;