10-99709472-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_020354.5(ENTPD7):​c.*4789T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00339 in 985,402 control chromosomes in the GnomAD database, including 19 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 0.0045 ( 5 hom., cov: 32)
Exomes 𝑓: 0.0032 ( 14 hom. )

Consequence

ENTPD7
NM_020354.5 3_prime_UTR

Scores

2

Clinical Significance

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

Conservation

PhyloP100: 0.226
Variant links:
Genes affected
ENTPD7 (HGNC:19745): (ectonucleoside triphosphate diphosphohydrolase 7) This gene encodes a purine-converting ectoenzyme which belongs to the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) family. The encoded protein hydrolyzes extracellular nucleoside triphosphates (UTP, GTP, and CTP) to nucleoside monophosphates as part of a purinergic signaling pathway. It contains two transmembrane domains at the N- and C-termini and a large, hydrophobic catalytic domain located in between. This gene affects oxidative stress as well as DNA damage and is a mediator of senescence. [provided by RefSeq, Mar 2017]
COX15 (HGNC:2263): (cytochrome c oxidase assembly homolog COX15) Cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. This component is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene encodes a protein which is not a structural subunit, but may be essential for the biogenesis of COX formation and may function in the hydroxylation of heme O, according to the yeast mutant studies. This protein is predicted to contain 5 transmembrane domains localized in the mitochondrial inner membrane. Alternative splicing of this gene generates two transcript variants diverging in the 3' region. [provided by RefSeq, Jul 2008]
CUTC (HGNC:24271): (cutC copper transporter) Members of the CUT family of copper transporters are associated with copper homeostasis and are involved in the uptake, storage, delivery, and efflux of copper (Gupta et al., 1995 [PubMed 7635807]; Li et al., 2005 [PubMed 16182249]).[supplied by OMIM, Mar 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 10-99709472-T-C is Benign according to our data. Variant chr10-99709472-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 878593.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00319 (2661/833098) while in subpopulation MID AF= 0.0216 (35/1620). AF 95% confidence interval is 0.016. There are 14 homozygotes in gnomad4_exome. There are 1237 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ENTPD7NM_020354.5 linkc.*4789T>C 3_prime_UTR_variant Exon 13 of 13 ENST00000370489.5 NP_065087.1 Q9NQZ7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ENTPD7ENST00000370489.5 linkc.*4789T>C 3_prime_UTR_variant Exon 13 of 13 1 NM_020354.5 ENSP00000359520.4 Q9NQZ7
ENSG00000285932ENST00000649102.1 linkn.*460+6876A>G intron_variant Intron 8 of 12 ENSP00000497114.1 A0A3B3IRX1
CUTCENST00000493385.5 linkn.116+6799T>C intron_variant Intron 1 of 4 3

Frequencies

GnomAD3 genomes
AF:
0.00446
AC:
679
AN:
152186
Hom.:
5
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00538
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00400
Gnomad ASJ
AF:
0.0233
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0147
Gnomad FIN
AF:
0.000659
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.00325
Gnomad OTH
AF:
0.00478
GnomAD4 exome
AF:
0.00319
AC:
2661
AN:
833098
Hom.:
14
Cov.:
31
AF XY:
0.00322
AC XY:
1237
AN XY:
384712
show subpopulations
Gnomad4 AFR exome
AF:
0.00450
Gnomad4 AMR exome
AF:
0.00305
Gnomad4 ASJ exome
AF:
0.0214
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0151
Gnomad4 FIN exome
AF:
0.00362
Gnomad4 NFE exome
AF:
0.00267
Gnomad4 OTH exome
AF:
0.00586
GnomAD4 genome
AF:
0.00446
AC:
680
AN:
152304
Hom.:
5
Cov.:
32
AF XY:
0.00452
AC XY:
337
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.00536
Gnomad4 AMR
AF:
0.00399
Gnomad4 ASJ
AF:
0.0233
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0151
Gnomad4 FIN
AF:
0.000659
Gnomad4 NFE
AF:
0.00325
Gnomad4 OTH
AF:
0.00473
Alfa
AF:
0.00607
Hom.:
0
Bravo
AF:
0.00433
Asia WGS
AF:
0.00231
AC:
8
AN:
3476

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Leigh syndrome Uncertain:1
Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not provided Benign:1
May 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

ENTPD7: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
4.1
DANN
Benign
0.40

Splicing

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.

Other links and lift over

dbSNP: rs148302095; hg19: chr10-101469229; API