NM_001248.4:c.812T>A

Variant names:

• chr3-40416054-T-A
• rs193921050
• NM_001248.4:c.812T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001248.4(ENTPD3):​c.812T>A​(p.Phe271Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENTPD3 NM_001248.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.92
• Publications: 3 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]

EIF1B-AS1 (HGNC:):

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD3	NM_001248.4	MANE Select	c.812T>A	p.Phe271Tyr	missense	Exon 7 of 11	NP_001239.2
	ENTPD3	NM_001291960.2		c.812T>A	p.Phe271Tyr	missense	Exon 7 of 11	NP_001278889.1
	ENTPD3	NM_001291961.2		c.812T>A	p.Phe271Tyr	missense	Exon 7 of 11	NP_001278890.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD3	ENST00000301825.8	TSL:1 MANE Select	c.812T>A	p.Phe271Tyr	missense	Exon 7 of 11	ENSP00000301825.3
	ENTPD3	ENST00000456402.5	TSL:1	c.812T>A	p.Phe271Tyr	missense	Exon 7 of 11	ENSP00000401565.1
	ENTPD3	ENST00000445129.1	TSL:1	c.812T>A	p.Phe271Tyr	missense	Exon 6 of 10	ENSP00000404671.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.046	T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0047	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		7.9
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.19
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.078	T
Polyphen		0.71	P
Vest4		0.61
MutPred		0.54		Gain of phosphorylation at F271 (P = 0.0588)
MVP		0.57
MPC		0.11
ClinPred		0.82	D
GERP RS		5.4
Varity_R		0.43
gMVP		0.58
Mutation Taster		=82/18	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: rs193921050; hg19: chr3-40457545; COSMIC: COSV57195689;