1-234373657-C-G

Position:

chr1-234373657-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001206641.3(COA6):c.191C>G(p.Ala64Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00271 in 1,612,910 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 46 hom. )

Consequence

COA6
NM_001206641.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0600

Variant links:

Genes affected

COA6 (HGNC:18025): (cytochrome c oxidase assembly factor 6) This gene encodes a member of the cytochrome c oxidase subunit 6B family. The encoded protein associates with cytochrome c oxidase may act has an cytochrome c oxidase mitochondrial respiratory complex VI assembly factor. Mutations in this gene may be associated with fatal infantile cardiomyopathy. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]

COA6 links:

COA6-AS1 (HGNC:40825): (COA6 antisense RNA 1)

COA6-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026690662).

BP6

Variant 1-234373657-C-G is Benign according to our data. Variant chr1-234373657-C-G is described in ClinVar as [Benign]. Clinvar id is 506753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00433 (659/152316) while in subpopulation EAS AF= 0.0195 (101/5188). AF 95% confidence interval is 0.0164. There are 6 homozygotes in gnomad4. There are 430 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
COA6	NM_001206641.3 linkuse as main transcript	c.191C>G	p.Ala64Gly	missense_variant	1/3	ENST00000366615.10	NP_001193570.2
COA6	NM_001012985.2 linkuse as main transcript			upstream_gene_variant			NP_001013003.1
COA6	NM_001301733.1 linkuse as main transcript			upstream_gene_variant			NP_001288662.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COA6	ENST00000366615.10 linkuse as main transcript	c.191C>G	p.Ala64Gly	missense_variant	1/3	1	NM_001206641.3	ENSP00000355574		Q5JTJ3-2
COA6-AS1	ENST00000685022.2 linkuse as main transcript	n.8G>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.00433

AC:

659

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00706

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0196

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.0305

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00128

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00725

AC:

1795

AN:

247622

Hom.:

AF XY:

0.00648

AC XY:

871

AN XY:

134344

show subpopulations

Gnomad AFR exome

AF:

0.000897

Gnomad AMR exome

AF:

0.0182

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0182

Gnomad SAS exome

AF:

0.00131

Gnomad FIN exome

AF:

0.0283

Gnomad NFE exome

AF:

0.00130

Gnomad OTH exome

AF:

0.00396

GnomAD4 exome

AF:

0.00254

AC:

3709

AN:

1460594

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

1740

AN XY:

726444

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.0160

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0195

Gnomad4 SAS exome

AF:

0.00138

Gnomad4 FIN exome

AF:

0.0264

Gnomad4 NFE exome

AF:

0.000478

Gnomad4 OTH exome

AF:

0.00245

GnomAD4 genome

AF:

0.00433

AC:

659

AN:

152316

Hom.:

Cov.:

AF XY:

0.00577

AC XY:

430

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00705

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0195

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.0305

Gnomad4 NFE

AF:

0.00129

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00112

Hom.:

Bravo

AF:

0.00268

ExAC

AF:

0.00636

AC:

772

Asia WGS

AF:

0.00924

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 22, 2017

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

COA6-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 04, 2019

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_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.70

CADD

Benign

8.0

DANN

Benign

0.93

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.38

MetaRNN

Benign

0.0027

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PROVEAN

Benign

-0.29

REVEL

Benign

0.022

Sift

Uncertain

0.026

Sift4G

Benign

0.30

Vest4

0.11

MVP

0.37

ClinPred

0.0028

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.051

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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