10-95847652-C-T

Variant names:

• chr10-95847652-C-T
• rs149326648
• NM_001776.6:c.1020C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001776.6(ENTPD1):​c.1020C>T​(p.Tyr340Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000681 in 1,614,246 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 0.00089 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00066 (4 hom.)
• Consequence: ENTPD1 NM_001776.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.31
• Publications: 0 publications found

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

ENSG00000240527 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 10-95847652-C-T is Benign according to our data. Variant chr10-95847652-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 541703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.31 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000893 (136/152364) while in subpopulation AMR AF = 0.00477 (73/15306). AF 95% confidence interval is 0.00389. There are 1 homozygotes in GnomAd4. There are 69 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001776.6. 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
	ENTPD1	NM_001776.6	MANE Select	c.1020C>T	p.Tyr340Tyr	synonymous	Exon 7 of 10	NP_001767.3
	ENTPD1	NM_001440932.1		c.1098C>T	p.Tyr366Tyr	synonymous	Exon 7 of 10	NP_001427861.1
	ENTPD1	NM_001164178.1		c.1056C>T	p.Tyr352Tyr	synonymous	Exon 7 of 10	NP_001157650.1	P49961-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD1	ENST00000371205.5	TSL:1 MANE Select	c.1020C>T	p.Tyr340Tyr	synonymous	Exon 7 of 10	ENSP00000360248.4	P49961-1
	ENTPD1	ENST00000453258.6	TSL:1	c.1041C>T	p.Tyr347Tyr	synonymous	Exon 7 of 10	ENSP00000390955.2	P49961-2
	ENTPD1	ENST00000635076.1	TSL:1	n.*595C>T		non_coding_transcript_exon	Exon 5 of 8	ENSP00000489250.1	A0A0U1RQZ5

Frequencies

GnomAD3 genomes AF: 0.000893 AC: 136 AN: 152246 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00115 AC: 288 AN: 251468 AF XY: 0.00110

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00280

Gnomad ASJ exome AF: 0.00258

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00103

Gnomad OTH exome AF: 0.00456

GnomAD4 exome AF: 0.000659 AC: 963 AN: 1461882 Hom.: 4 Cov.: 33 AF XY: 0.000664 AC XY: 483 AN XY: 727244

African (AFR) AF: 0.000299 AC: 10 AN: 33480

American (AMR) AF: 0.00367 AC: 164 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 60 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000626 AC: 54 AN: 86258

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53420

Middle Eastern (MID) AF: 0.0118 AC: 68 AN: 5768

European-Non Finnish (NFE) AF: 0.000454 AC: 505 AN: 1112004

Other (OTH) AF: 0.00166 AC: 100 AN: 60396

GnomAD4 genome AF: 0.000893 AC: 136 AN: 152364 Hom.: 1 Cov.: 32 AF XY: 0.000926 AC XY: 69 AN XY: 74512

African (AFR) AF: 0.000216 AC: 9 AN: 41588

American (AMR) AF: 0.00477 AC: 73 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10628

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68032

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.000948 Hom.: 2

Bravo AF: 0.00133

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hereditary spastic paraplegia (1)
-	-	1	Hereditary spastic paraplegia 64 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	4.5
DANN	Benign	0.55
PhyloP100		1.3
Mutation Taster		=100/0	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: rs149326648; hg19: chr10-97607409; COSMIC: COSV64602600; COSMIC: COSV64602600;