Genetic Variant ENTPD1:p.Val9Leu (chr10-95823245-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001440938.1(ENTPD1):c.-300G>C 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 0.000000684 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ENTPD1
NM_001440938.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.300

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060097724).

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>C	p.Val9Leu	missense	Exon 2 of 10	NP_001767.3
ENTPD1	NM_001440938.1		c.-300G>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 10	NP_001427867.1
ENTPD1	NM_001164182.2		c.-239G>C		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>C	p.Val9Leu	missense	Exon 2 of 10	ENSP00000360248.4	P49961-1
ENTPD1	ENST00000453258.6	TSL:1	c.46G>C	p.Val16Leu	missense	Exon 2 of 10	ENSP00000390955.2	P49961-2
ENTPD1	ENST00000635076.1	TSL:1	n.25G>C		non_coding_transcript_exon	Exon 2 of 8	ENSP00000489250.1	A0A0U1RQZ5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461712

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727138

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

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:

8.99e-7

AC:

AN:

1111920

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

3.7

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.17

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.74

M_CAP

Benign

0.0021

MetaRNN

Benign

0.060

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.34

PhyloP100

0.30

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.47

REVEL

Benign

0.052

Sift

Benign

0.56

Sift4G

Benign

0.56

Polyphen

0.011

Vest4

0.13

MutPred

0.13

Loss of methylation at K5 (P = 0.0798)

MVP

0.10

MPC

0.16

ClinPred

0.055

GERP RS

-0.87

Varity_R

0.074

gMVP

0.20

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over