rs3793744

chr10-95847509-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001776.6(ENTPD1):c.877G>A(p.Val293Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00343 in 1,614,134 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (78 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (67 hom.)
• Consequence: ENTPD1 NM_001776.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.254

Genes affected

ENTPD1 (HGNC:3363): (ectonucleoside triphosphate diphosphohydrolase 1) The protein encoded by this gene is a plasma membrane protein that hydrolyzes extracellular ATP and ADP to AMP. Inhibition of this protein's activity may confer anticancer benefits. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

(HGNC:):

ENTPD1-AS1 (HGNC:45203): (ENTPD1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022000968).
• BP6: Variant 10-95847509-G-A is Benign according to our data. Variant chr10-95847509-G-A is described in ClinVar as [Benign]. Clinvar id is 703843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENTPD1	NM_001776.6	c.877G>A	p.Val293Ile	missense_variant	7/10	ENST00000371205.5
ENTPD1-AS1	NR_038444.1	n.440-24C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENTPD1	ENST00000371205.5	c.877G>A	p.Val293Ile	missense_variant	7/10	1	NM_001776.6	P1
	ENST00000433113.1	n.260+13742G>A		intron_variant, non_coding_transcript_variant		2
ENTPD1-AS1	ENST00000669711.1	n.443+29009C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0170 AC: 2594 AN: 152150 Hom.: 74 Cov.: 32

Gnomad AFR AF: 0.0573

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00628

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0148

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0158

GnomAD3 exomes AF: 0.00548 AC: 1379 AN: 251430 Hom.: 31 AF XY: 0.00406 AC XY: 552 AN XY: 135884

Gnomad AFR exome AF: 0.0581

Gnomad AMR exome AF: 0.00266

Gnomad ASJ exome AF: 0.000794

Gnomad EAS exome AF: 0.0158

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000211

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00200 AC: 2917 AN: 1461866 Hom.: 67 Cov.: 33 AF XY: 0.00173 AC XY: 1260 AN XY: 727236

Gnomad4 AFR exome AF: 0.0566

Gnomad4 AMR exome AF: 0.00291

Gnomad4 ASJ exome AF: 0.000574

Gnomad4 EAS exome AF: 0.0111

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000104

Gnomad4 OTH exome AF: 0.00470

GnomAD4 genome AF: 0.0172 AC: 2615 AN: 152268 Hom.: 78 Cov.: 32 AF XY: 0.0168 AC XY: 1251 AN XY: 74444

Gnomad4 AFR AF: 0.0576

Gnomad4 AMR AF: 0.00627

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.0149

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.00432 Hom.: 17

Bravo AF: 0.0192

ESP6500AA AF: 0.0601 AC: 265

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.00631 AC: 766

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

ENTPD1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 03, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Hereditary spastic paraplegia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jan 17, 2022

- -

Hereditary spastic paraplegia 64 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 24, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.029
Dann	Benign	0.60
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.55	T;T;T;T
MetaRNN	Benign	0.0022	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.070	N;N;N;N
REVEL	Benign	0.019
Sift	Benign	0.50	T;T;T;T
Sift4G	Benign	0.52	T;T;T;T
Polyphen		0.0040	B;.;.;B
Vest4		0.030
MVP		0.082
MPC		0.13
ClinPred		0.00030	T
GERP RS		-5.7
Varity_R		0.019
gMVP		0.41

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

Other links and lift over

dbSNP: rs3793744; hg19: chr10-97607266; COSMIC: COSV64601433; COSMIC: COSV64601433;