Variant 9-137436005-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001033113.2(ENTPD8):c.1050+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00523 in 1,612,536 control chromosomes in the GnomAD database, including 341 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 160 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 181 hom. )

Consequence

ENTPD8
NM_001033113.2 splice_region, intron

Scores

Splicing: ADA: 0.0004549

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.101

Variant links:

Genes affected

ENTPD8 (HGNC:24860): (ectonucleoside triphosphate diphosphohydrolase 8) Predicted to enable guanosine-diphosphatase activity and uridine-diphosphatase activity. Predicted to be involved in nucleoside diphosphate catabolic process. Predicted to act upstream of or within nucleoside diphosphate biosynthetic process and nucleoside monophosphate biosynthetic process. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENTPD8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 9-137436005-G-A is Benign according to our data. Variant chr9-137436005-G-A is described in ClinVar as [Benign]. Clinvar id is 776486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENTPD8	NM_001033113.2 linkuse as main transcript	c.1050+8C>T		splice_region_variant, intron_variant		ENST00000371506.7	NP_001028285.1
ENTPD8	NM_198585.3 linkuse as main transcript	c.1050+8C>T		splice_region_variant, intron_variant			NP_940987.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
ENTPD8	ENST00000371506.7 linkuse as main transcript	c.1050+8C>T	splice_region_variant, intron_variant	5	NM_001033113.2	ENSP00000360561	P1	Q5MY95-1
ENTPD8	ENST00000344119.6 linkuse as main transcript	c.1050+8C>T	splice_region_variant, intron_variant	1		ENSP00000344089		Q5MY95-2
ENTPD8	ENST00000461823.1 linkuse as main transcript	n.1848+8C>T	splice_region_variant, intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0259

AC:

3945

AN:

152216

Hom.:

160

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0885

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0114

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.0249

GnomAD3 exomes

AF:

0.00688

AC:

1711

AN:

248816

Hom.:

AF XY:

0.00527

AC XY:

712

AN XY:

135164

show subpopulations

Gnomad AFR exome

AF:

0.0925

Gnomad AMR exome

AF:

0.00400

Gnomad ASJ exome

AF:

0.000905

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000581

Gnomad OTH exome

AF:

0.00362

GnomAD4 exome

AF:

0.00307

AC:

4490

AN:

1460202

Hom.:

181

Cov.:

AF XY:

0.00263

AC XY:

1910

AN XY:

726374

show subpopulations

Gnomad4 AFR exome

AF:

0.0979

Gnomad4 AMR exome

AF:

0.00523

Gnomad4 ASJ exome

AF:

0.00126

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.0000768

Gnomad4 NFE exome

AF:

0.000423

Gnomad4 OTH exome

AF:

0.00671

GnomAD4 genome

AF:

0.0259

AC:

3946

AN:

152334

Hom.:

160

Cov.:

AF XY:

0.0248

AC XY:

1844

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0883

Gnomad4 AMR

AF:

0.0114

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.0134

Hom.:

Bravo

AF:

0.0293

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.0

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00045

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over