10-99711101-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020354.5(ENTPD7):c.*6426dup variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 975,856 control chromosomes in the GnomAD database, including 352,993 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.83 (52620 hom., cov: 0)
  • Exomes 𝑓: 0.85 (300373 hom.)
• Consequence: ENTPD7 NM_020354.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.217

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 10-99711101-C-CA is Benign according to our data. Variant chr10-99711101-C-CA is described in ClinVar as [Benign]. Clinvar id is 298385.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENTPD7	NM_020354.5	c.*6426dup		3_prime_UTR_variant	13/13	ENST00000370489.5
COX15	NM_078470.6	c.*3485_*3486insT		3_prime_UTR_variant	9/9	ENST00000016171.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COX15	ENST00000016171.6	c.*3485_*3486insT		3_prime_UTR_variant	9/9	1	NM_078470.6	P1
ENTPD7	ENST00000370489.5	c.*6426dup		3_prime_UTR_variant	13/13	1	NM_020354.5	P1
CUTC	ENST00000493385.5	n.116+8436dup		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.831 AC: 125985 AN: 151524 Hom.: 52594 Cov.: 0

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.812

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.828

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.920

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.841

GnomAD4 exome AF: 0.854 AC: 703537 AN: 824218 Hom.: 300373 Cov.: 30 AF XY: 0.854 AC XY: 324995 AN XY: 380754

Gnomad4 AFR exome AF: 0.743

Gnomad4 AMR exome AF: 0.879

Gnomad4 ASJ exome AF: 0.819

Gnomad4 EAS exome AF: 0.787

Gnomad4 SAS exome AF: 0.863

Gnomad4 FIN exome AF: 0.854

Gnomad4 NFE exome AF: 0.856

Gnomad4 OTH exome AF: 0.848

GnomAD4 genome AF: 0.831 AC: 126068 AN: 151638 Hom.: 52620 Cov.: 0 AF XY: 0.832 AC XY: 61616 AN XY: 74066

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.861

Gnomad4 ASJ AF: 0.828

Gnomad4 EAS AF: 0.786

Gnomad4 SAS AF: 0.864

Gnomad4 FIN AF: 0.879

Gnomad4 NFE AF: 0.865

Gnomad4 OTH AF: 0.838

Alfa AF: 0.827 Hom.: 1702

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Mitochondrial complex IV deficiency, nuclear type 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11405417; hg19: chr10-101470858;