3-40411942-G-A

Variant names:

• chr3-40411942-G-A
• rs41286046
• NM_001248.4:c.417G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001248.4(ENTPD3):​c.417G>A​(p.Thr139Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,610,908 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (5 hom.)
• Consequence: ENTPD3 NM_001248.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.57
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 3-40411942-G-A is Benign according to our data. Variant chr3-40411942-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2653691.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.57 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 5 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.417G>A	p.Thr139Thr	synonymous	Exon 5 of 11	NP_001239.2	O75355-1
	ENTPD3	NM_001291960.2		c.417G>A	p.Thr139Thr	synonymous	Exon 5 of 11	NP_001278889.1	O75355-1
	ENTPD3	NM_001291961.2		c.417G>A	p.Thr139Thr	synonymous	Exon 5 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.417G>A	p.Thr139Thr	synonymous	Exon 5 of 11	ENSP00000301825.3	O75355-1
	ENTPD3	ENST00000456402.5	TSL:1	c.417G>A	p.Thr139Thr	synonymous	Exon 5 of 11	ENSP00000401565.1	O75355-1
	ENTPD3	ENST00000445129.1	TSL:1	c.417G>A	p.Thr139Thr	synonymous	Exon 4 of 10	ENSP00000404671.1	O75355-2

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 193 AN: 152080 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00223

Gnomad OTH AF: 0.000961

GnomAD2 exomes AF: 0.00122 AC: 302 AN: 247290 AF XY: 0.00123

Gnomad AFR exome AF: 0.000556

Gnomad AMR exome AF: 0.000633

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000186

Gnomad NFE exome AF: 0.00233

Gnomad OTH exome AF: 0.00117

GnomAD4 exome AF: 0.00185 AC: 2702 AN: 1458710 Hom.: 5 Cov.: 31 AF XY: 0.00180 AC XY: 1309 AN XY: 725518

African (AFR) AF: 0.000449 AC: 15 AN: 33426

American (AMR) AF: 0.000747 AC: 33 AN: 44168

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39580

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85352

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00229 AC: 2549 AN: 1110712

Other (OTH) AF: 0.00149 AC: 90 AN: 60292

GnomAD4 genome AF: 0.00127 AC: 193 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.00120 AC XY: 89 AN XY: 74428

African (AFR) AF: 0.000554 AC: 23 AN: 41534

American (AMR) AF: 0.000719 AC: 11 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10604

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

European-Non Finnish (NFE) AF: 0.00223 AC: 152 AN: 68016

Other (OTH) AF: 0.000951 AC: 2 AN: 2104

Alfa AF: 0.00182 Hom.: 1

Bravo AF: 0.00136

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
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.49
DANN	Benign	0.83
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs41286046; hg19: chr3-40453433;