GeneBe

rs149326648

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_001776.6(ENTPD1):​c.1020C>G​(p.Tyr340*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Y340Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

ENTPD1
NM_001776.6 stop_gained

Scores

2
3
1

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.31

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

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ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 12 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 10-95847652-C-G is Pathogenic according to our data. Variant chr10-95847652-C-G is described in ClinVar as Pathogenic. ClinVar VariationId is 2129367.Status of the report is criteria_provided_single_submitter, 1 stars.

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.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ENTPD1
NM_001776.6
MANE Select
c.1020C>Gp.Tyr340*
stop_gained
Exon 7 of 10NP_001767.3
ENTPD1
NM_001440932.1
c.1098C>Gp.Tyr366*
stop_gained
Exon 7 of 10NP_001427861.1
ENTPD1
NM_001164178.1
c.1056C>Gp.Tyr352*
stop_gained
Exon 7 of 10NP_001157650.1P49961-6

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ENTPD1
ENST00000371205.5
TSL:1 MANE Select
c.1020C>Gp.Tyr340*
stop_gained
Exon 7 of 10ENSP00000360248.4P49961-1
ENTPD1
ENST00000453258.6
TSL:1
c.1041C>Gp.Tyr347*
stop_gained
Exon 7 of 10ENSP00000390955.2P49961-2
ENTPD1
ENST00000635076.1
TSL:1
n.*595C>G
non_coding_transcript_exon
Exon 5 of 8ENSP00000489250.1A0A0U1RQZ5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251468
AF XY:
0.00000736
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

ClinVar submissions
Significance:Pathogenic
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
1
-
-
Hereditary spastic paraplegia 64 (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.60
D
BayesDel_noAF
Pathogenic
0.54
CADD
Pathogenic
34
DANN
Uncertain
1.0
Eigen
Uncertain
0.24
Eigen_PC
Benign
0.046
FATHMM_MKL
Uncertain
0.88
D
PhyloP100
1.3
Vest4
0.53
GERP RS
2.8
Mutation Taster
=14/186
disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs149326648; hg19: chr10-97607409; API