17-14069638-C-T

Position:

chr17-14069638-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The ENST00000261643.8(COX10):c.33C>T(p.Arg11=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0663 in 1,613,798 control chromosomes in the GnomAD database, including 3,999 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 291 hom., cov: 32)

Exomes 𝑓: 0.068 ( 3708 hom. )

Consequence

COX10
ENST00000261643.8 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.20

Variant links:

Genes affected

COX10 (HGNC:2260): (cytochrome c oxidase assembly factor heme A:farnesyltransferase COX10) 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 heme A:farnesyltransferase, which is not a structural subunit but required for the expression of functional COX and functions in the maturation of the heme A prosthetic group of COX. This protein is predicted to contain 7-9 transmembrane domains localized in the mitochondrial inner membrane. A gene mutation, which results in the substitution of a lysine for an asparagine (N204K), is identified to be responsible for cytochrome c oxidase deficiency. In addition, this gene is disrupted in patients with CMT1A (Charcot-Marie-Tooth type 1A) duplication and with HNPP (hereditary neuropathy with liability to pressure palsies) deletion. [provided by RefSeq, Jul 2008]

COX10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 17-14069638-C-T is Benign according to our data. Variant chr17-14069638-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 137005.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.2 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.073 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX10	NM_001303.4 linkuse as main transcript	c.33C>T	p.Arg11=	synonymous_variant	1/7	ENST00000261643.8	NP_001294.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COX10	ENST00000261643.8 linkuse as main transcript	c.33C>T	p.Arg11=	synonymous_variant	1/7	1	NM_001303.4	ENSP00000261643	P1	Q12887-1

Frequencies

GnomAD3 genomes

AF:

0.0542

AC:

8242

AN:

152168

Hom.:

291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0434

Gnomad ASJ

AF:

0.0542

Gnomad EAS

AF:

0.0280

Gnomad SAS

AF:

0.0373

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0747

Gnomad OTH

AF:

0.0546

GnomAD3 exomes

AF:

0.0589

AC:

14639

AN:

248538

Hom.:

557

AF XY:

0.0602

AC XY:

8105

AN XY:

134632

show subpopulations

Gnomad AFR exome

AF:

0.0101

Gnomad AMR exome

AF:

0.0269

Gnomad ASJ exome

AF:

0.0572

Gnomad EAS exome

AF:

0.0308

Gnomad SAS exome

AF:

0.0408

Gnomad FIN exome

AF:

0.131

Gnomad NFE exome

AF:

0.0715

Gnomad OTH exome

AF:

0.0639

GnomAD4 exome

AF:

0.0675

AC:

98720

AN:

1461512

Hom.:

3708

Cov.:

AF XY:

0.0670

AC XY:

48693

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.00917

Gnomad4 AMR exome

AF:

0.0289

Gnomad4 ASJ exome

AF:

0.0590

Gnomad4 EAS exome

AF:

0.0258

Gnomad4 SAS exome

AF:

0.0405

Gnomad4 FIN exome

AF:

0.133

Gnomad4 NFE exome

AF:

0.0720

Gnomad4 OTH exome

AF:

0.0623

GnomAD4 genome

AF:

0.0541

AC:

8240

AN:

152286

Hom.:

291

Cov.:

AF XY:

0.0557

AC XY:

4148

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0118

Gnomad4 AMR

AF:

0.0434

Gnomad4 ASJ

AF:

0.0542

Gnomad4 EAS

AF:

0.0279

Gnomad4 SAS

AF:

0.0371

Gnomad4 FIN

AF:

0.129

Gnomad4 NFE

AF:

0.0747

Gnomad4 OTH

AF:

0.0540

Alfa

AF:

0.0636

Hom.:

417

Bravo

AF:

0.0448

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

EpiCase

AF:

0.0668

EpiControl

AF:

0.0665

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 23, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 30, 2014

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Leigh syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Mitochondrial complex IV deficiency, nuclear type 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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