rs145994698

Variant names:

• chr10-95866183-G-C
• rs145994698
• NM_001776.6:c.1333G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-95866183-G-C
• chr10-95866183-G-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS1_Supporting

The NM_001776.6(ENTPD1):​c.1333G>C​(p.Gly445Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000795 in 1,613,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00045 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00083 (0 hom.)
• Consequence: ENTPD1 NM_001776.6 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 0.953
• Publications: 6 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]

ENSG00000270099 (HGNC:):

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

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000447 (68/152232) while in subpopulation NFE AF = 0.000838 (57/68026). AF 95% confidence interval is 0.000664. There are 0 homozygotes in GnomAd4. There are 34 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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.1333G>C	p.Gly445Arg	missense	Exon 10 of 10	NP_001767.3
	ENTPD1	NM_001440932.1		c.1411G>C	p.Gly471Arg	missense	Exon 10 of 10	NP_001427861.1
	ENTPD1	NM_001164178.1		c.1369G>C	p.Gly457Arg	missense	Exon 10 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.1333G>C	p.Gly445Arg	missense	Exon 10 of 10	ENSP00000360248.4	P49961-1
	ENTPD1	ENST00000453258.6	TSL:1	c.1354G>C	p.Gly452Arg	missense	Exon 10 of 10	ENSP00000390955.2	P49961-2
	ENTPD1	ENST00000635076.1	TSL:1	n.*908G>C		non_coding_transcript_exon	Exon 8 of 8	ENSP00000489250.1	A0A0U1RQZ5

Frequencies

GnomAD3 genomes AF: 0.000447 AC: 68 AN: 152114 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000838

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000445 AC: 111 AN: 249468 AF XY: 0.000482

Gnomad AFR exome AF: 0.000186

Gnomad AMR exome AF: 0.000465

Gnomad ASJ exome AF: 0.0000996

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000798

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000832 AC: 1215 AN: 1461202 Hom.: 0 Cov.: 31 AF XY: 0.000865 AC XY: 629 AN XY: 726832

African (AFR) AF: 0.000179 AC: 6 AN: 33470

American (AMR) AF: 0.000470 AC: 21 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86146

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53356

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5764

European-Non Finnish (NFE) AF: 0.00104 AC: 1161 AN: 1111688

Other (OTH) AF: 0.000348 AC: 21 AN: 60364

GnomAD4 genome AF: 0.000447 AC: 68 AN: 152232 Hom.: 0 Cov.: 32 AF XY: 0.000457 AC XY: 34 AN XY: 74414

African (AFR) AF: 0.000120 AC: 5 AN: 41544

American (AMR) AF: 0.000392 AC: 6 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000838 AC: 57 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000726 Hom.: 0

Bravo AF: 0.000404

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.000412 AC: 50

EpiCase AF: 0.000763

EpiControl AF: 0.000715

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.088
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.95
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.075
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.040	D
Polyphen		0.90	P
Vest4		0.11
MVP		0.18
MPC		0.20
ClinPred		0.046	T
GERP RS		2.0
Varity_R		0.20
gMVP		0.54
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: -6

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

Other links and lift over

dbSNP: rs145994698; hg19: chr10-97625940;