dbSNP rs150772804: ENTPD1:p.Val9Met (chr10-95823245-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001440938.1(ENTPD1):c.-300G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000961 in 1,614,030 control chromosomes in the GnomAD database, including 3 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 0.00057 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 2 hom. )

Consequence

ENTPD1
NM_001440938.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:1O:1

Conservation

PhyloP100: 0.300

Publications

5 publications found

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:

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

ENTPD1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03844744).

BP6

Variant 10-95823245-G-A is Benign according to our data. Variant chr10-95823245-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 374088.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000571 (87/152322) while in subpopulation NFE AF = 0.00104 (71/68028). AF 95% confidence interval is 0.000848. There are 1 homozygotes in GnomAd4. There are 34 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001440938.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENTPD1	NM_001776.6	MANE Select	c.25G>A	p.Val9Met	missense	Exon 2 of 10	NP_001767.3
ENTPD1	NM_001440938.1		c.-300G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 10	NP_001427867.1
ENTPD1	NM_001164182.2		c.-239G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	NP_001157654.1	P49961-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENTPD1	ENST00000371205.5	TSL:1 MANE Select	c.25G>A	p.Val9Met	missense	Exon 2 of 10	ENSP00000360248.4	P49961-1
ENTPD1	ENST00000453258.6	TSL:1	c.46G>A	p.Val16Met	missense	Exon 2 of 10	ENSP00000390955.2	P49961-2
ENTPD1	ENST00000635076.1	TSL:1	n.25G>A		non_coding_transcript_exon	Exon 2 of 8	ENSP00000489250.1	A0A0U1RQZ5

Frequencies

GnomAD3 genomes

AF:

0.000572

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000501

AC:

126

AN:

251322

AF XY:

0.000486

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000933

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.00100

AC:

1464

AN:

1461708

Hom.:

Cov.:

AF XY:

0.000926

AC XY:

673

AN XY:

727134

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33476

American (AMR)

AF:

0.000268

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00126

AC:

1404

AN:

1111916

Other (OTH)

AF:

0.000712

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

155

233

310

388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000571

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.000216

AC:

AN:

41574

American (AMR)

AF:

0.000327

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00104

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000794

Hom.:

Bravo

AF:

0.000650

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000379

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary spastic paraplegia (1)

Hereditary spastic paraplegia 64 (2)

not provided (1)

Polymicrogyria;C0557874:Global developmental delay;C4551563:Microcephaly (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.11

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0049

MetaRNN

Benign

0.038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

0.30

PrimateAI

Benign

0.37

PROVEAN

Benign

0.040

REVEL

Benign

0.099

Sift

Benign

0.043

Sift4G

Benign

0.16

Polyphen

0.98

Vest4

0.18

MVP

0.093

MPC

0.43

ClinPred

0.024

GERP RS

-0.87

Varity_R

0.066

gMVP

0.17

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over