19-35651285-C-T

Position:

chr19-35651285-C-T

Variant summary

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

The NM_001863.5(COX6B1):c.42C>T(p.Thr14Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 1,613,176 control chromosomes in the GnomAD database, including 9,699 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1610 hom., cov: 31)

Exomes 𝑓: 0.094 ( 8089 hom. )

Consequence

COX6B1
NM_001863.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.40

Variant links:

Genes affected

COX6B1 (HGNC:2280): (cytochrome c oxidase subunit 6B1) Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. It 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 be involved in the regulation and assembly of the complex. This nuclear gene encodes subunit VIb. Mutations in this gene are associated with severe infantile encephalomyopathy. Three pseudogenes COX6BP-1, COX6BP-2 and COX6BP-3 have been found on chromosomes 7, 17 and 22q13.1-13.2, respectively. [provided by RefSeq, Jan 2010]

COX6B1 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=-0.35).

BP6

Variant 19-35651285-C-T is Benign according to our data. Variant chr19-35651285-C-T is described in ClinVar as [Benign]. Clinvar id is 137022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.4 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX6B1	NM_001863.5 link	c.42C>T	p.Thr14Thr	synonymous_variant	2/4	ENST00000649813.2	NP_001854.1	P14854

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COX6B1	ENST00000649813.2 link	c.42C>T	p.Thr14Thr	synonymous_variant	2/4		NM_001863.5	ENSP00000497926.1		P14854

Frequencies

GnomAD3 genomes

AF:

0.131

AC:

19940

AN:

151912

Hom.:

1599

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.0605

Gnomad EAS

AF:

0.291

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0772

Gnomad OTH

AF:

0.113

GnomAD3 exomes

AF:

0.122

AC:

30642

AN:

251458

Hom.:

2424

AF XY:

0.118

AC XY:

16041

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.203

Gnomad AMR exome

AF:

0.150

Gnomad ASJ exome

AF:

0.0613

Gnomad EAS exome

AF:

0.282

Gnomad SAS exome

AF:

0.133

Gnomad FIN exome

AF:

0.132

Gnomad NFE exome

AF:

0.0771

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.0936

AC:

136708

AN:

1461146

Hom.:

8089

Cov.:

AF XY:

0.0936

AC XY:

68008

AN XY:

726928

show subpopulations

Gnomad4 AFR exome

AF:

0.212

Gnomad4 AMR exome

AF:

0.147

Gnomad4 ASJ exome

AF:

0.0601

Gnomad4 EAS exome

AF:

0.281

Gnomad4 SAS exome

AF:

0.129

Gnomad4 FIN exome

AF:

0.131

Gnomad4 NFE exome

AF:

0.0769

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.131

AC:

19980

AN:

152030

Hom.:

1610

Cov.:

AF XY:

0.136

AC XY:

10096

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.208

Gnomad4 AMR

AF:

0.136

Gnomad4 ASJ

AF:

0.0605

Gnomad4 EAS

AF:

0.290

Gnomad4 SAS

AF:

0.142

Gnomad4 FIN

AF:

0.132

Gnomad4 NFE

AF:

0.0772

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.0862

Hom.:

539

Bravo

AF:

0.135

Asia WGS

AF:

0.215

AC:

745

AN:

3478

EpiCase

AF:

0.0726

EpiControl

AF:

0.0728

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 22, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2011

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. -

Mitochondrial complex IV deficiency, nuclear type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

COX6B1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 22, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

9.8

DANN

Benign

0.61

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