chr10-99711101-C-CA

Variant names:

• chr10-99711101-C-CA
• rs11405417
• NM_020354.5:c.*6426dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020354.5(ENTPD7):​c.*6426dupA 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
• Publications: 2 publications found

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]

ENSG00000285932 (HGNC:):

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020354.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD7	NM_020354.5	MANE Select	c.*6426dupA		3_prime_UTR	Exon 13 of 13	NP_065087.1	Q9NQZ7
	COX15	NM_078470.6	MANE Select	c.*3485dupT		3_prime_UTR	Exon 9 of 9	NP_510870.1	Q7KZN9-1
	ENTPD7	NM_001349962.2		c.*6426dupA		3_prime_UTR	Exon 14 of 14	NP_001336891.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD7	ENST00000370489.5	TSL:1 MANE Select	c.*6426dupA		3_prime_UTR	Exon 13 of 13	ENSP00000359520.4	Q9NQZ7
	COX15	ENST00000016171.6	TSL:1 MANE Select	c.*3485dupT		3_prime_UTR	Exon 9 of 9	ENSP00000016171.6	Q7KZN9-1
	ENSG00000285932	ENST00000649102.1		n.*460+5246dupT		intron	N/A	ENSP00000497114.1	A0A3B3IRX1

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

African (AFR) AF: 0.743 AC: 11620 AN: 15648

American (AMR) AF: 0.879 AC: 853 AN: 970

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 4167 AN: 5088

East Asian (EAS) AF: 0.787 AC: 2835 AN: 3600

South Asian (SAS) AF: 0.863 AC: 14018 AN: 16242

European-Finnish (FIN) AF: 0.854 AC: 234 AN: 274

Middle Eastern (MID) AF: 0.886 AC: 1427 AN: 1610

European-Non Finnish (NFE) AF: 0.856 AC: 645446 AN: 753736

Other (OTH) AF: 0.848 AC: 22937 AN: 27050

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

African (AFR) AF: 0.755 AC: 31198 AN: 41346

American (AMR) AF: 0.861 AC: 13109 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.828 AC: 2870 AN: 3468

East Asian (EAS) AF: 0.786 AC: 4058 AN: 5164

South Asian (SAS) AF: 0.864 AC: 4153 AN: 4806

European-Finnish (FIN) AF: 0.879 AC: 9131 AN: 10392

Middle Eastern (MID) AF: 0.918 AC: 268 AN: 292

European-Non Finnish (NFE) AF: 0.865 AC: 58774 AN: 67916

Other (OTH) AF: 0.838 AC: 1771 AN: 2114

Alfa AF: 0.827 Hom.: 1702

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Mitochondrial complex IV deficiency, nuclear type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.22

Splicing

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

Other links and lift over

dbSNP: rs11405417; hg19: chr10-101470858;