Genetic Variant ENTPD1:p.Gln11Gln (chr10-95711989-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001098175.2(ENTPD1):c.33G>A(p.Gln11Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 1,613,846 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 21 hom. )

Consequence

ENTPD1
NM_001098175.2 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.280

Variant links:

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]

ENTPD1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 10-95711989-G-A is Benign according to our data. Variant chr10-95711989-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2498467.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}. Variant chr10-95711989-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.28 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00288 (439/152270) while in subpopulation NFE AF= 0.0052 (354/68024). AF 95% confidence interval is 0.00476. There are 1 homozygotes in gnomad4. There are 188 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
ENTPD1	NM_001098175.2 link	c.33G>A	p.Gln11Gln	synonymous_variant	Exon 1 of 10	NP_001091645.1	P49961-2
ENTPD1	XM_011540371.3 link	c.33G>A	p.Gln11Gln	synonymous_variant	Exon 3 of 12	XP_011538673.1	P49961-2
ENTPD1	XM_047426023.1 link	c.33G>A	p.Gln11Gln	synonymous_variant	Exon 4 of 13	XP_047281979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENTPD1	ENST00000453258.6 link	c.33G>A	p.Gln11Gln	synonymous_variant	Exon 1 of 10	1		ENSP00000390955.2		P49961-2

Frequencies

GnomAD3 genomes

AF:

0.00289

AC:

439

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00520

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00261

AC:

646

AN:

247138

Hom.:

AF XY:

0.00251

AC XY:

337

AN XY:

134302

show subpopulations

Gnomad AFR exome

AF:

0.000839

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000835

Gnomad NFE exome

AF:

0.00454

Gnomad OTH exome

AF:

0.00265

GnomAD4 exome

AF:

0.00498

AC:

7277

AN:

1461576

Hom.:

Cov.:

AF XY:

0.00488

AC XY:

3549

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.00279

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00107

Gnomad4 NFE exome

AF:

0.00616

Gnomad4 OTH exome

AF:

0.00361

GnomAD4 genome

AF:

0.00288

AC:

439

AN:

152270

Hom.:

Cov.:

AF XY:

0.00253

AC XY:

188

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00520

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00355

Hom.:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00431

EpiControl

AF:

0.00581

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Jul 05, 2023

Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ENTPD1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.7

DANN

Benign

0.56

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over