10-95711989-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The ENST00000453258.6(ENTPD1):c.33G>A(p.Gln11=) 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 ENST00000453258.6 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.280

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]

ACMG classification

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 GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENTPD1	NM_001098175.2	c.33G>A	p.Gln11=	synonymous_variant	1/10
ENTPD1	XM_011540371.3	c.33G>A	p.Gln11=	synonymous_variant	3/12
ENTPD1	XM_047426023.1	c.33G>A	p.Gln11=	synonymous_variant	4/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENTPD1	ENST00000453258.6	c.33G>A	p.Gln11=	synonymous_variant	1/10	1

Frequencies

GnomAD3 genomes AF: 0.00289 AC: 439 AN: 152152 Hom.: 1 Cov.: 32

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.: 3 AF XY: 0.00251 AC XY: 337 AN XY: 134302

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.: 21 Cov.: 30 AF XY: 0.00488 AC XY: 3549 AN XY: 727114

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.: 1 Cov.: 32 AF XY: 0.00253 AC XY: 188 AN XY: 74442

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.: 2

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00431

EpiControl AF: 0.00581

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1 Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	Jul 05, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	ENTPD1: 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

Other links and lift over

dbSNP: rs200247284; hg19: chr10-97471746;