Variant rs146440690 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001206641.3(COA6):c.349G>A(p.Glu117Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,840 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

COA6
NM_001206641.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.87

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COA6	NM_001206641.3 link	c.349G>A	p.Glu117Lys	missense_variant	2/3	ENST00000366615.10	NP_001193570.2	Q5JTJ3-2
COA6	NM_001012985.2 link	c.259G>A	p.Glu87Lys	missense_variant	2/3		NP_001013003.1	Q5JTJ3-1
COA6	NM_001301733.1 link	c.121G>A	p.Glu41Lys	missense_variant	1/2		NP_001288662.1	Q5JTJ3-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COA6	ENST00000366615.10 link	c.349G>A	p.Glu117Lys	missense_variant	2/3	1	NM_001206641.3	ENSP00000355574.5	Q5JTJ3-2
COA6	ENST00000366613.1 link	c.259G>A	p.Glu87Lys	missense_variant	2/3	1		ENSP00000355572.1	Q5JTJ3-1
COA6	ENST00000366612.1 link	c.121G>A	p.Glu41Lys	missense_variant	1/2	1		ENSP00000355571.1	Q5JTJ3-3
COA6	ENST00000619305.1 link	c.121G>A	p.Glu41Lys	missense_variant	2/3	1		ENSP00000479686.1	Q5JTJ3-3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461762

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Uncertain

0.030

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.74

.;.;D;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.88

D;D;D;.

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.48

T;T;T;T

MetaSVM

Uncertain

-0.0059

MutationAssessor

Uncertain

2.2

.;.;M;.

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.1

D;.;D;D

REVEL

Uncertain

0.43

Sift

Uncertain

0.015

D;.;D;D

Sift4G

Uncertain

0.040

D;T;T;T

Polyphen

0.95

.;.;P;.

Vest4

0.45

MutPred

0.40

.;.;Gain of MoRF binding (P = 0.0025);.;

MVP

0.89

MPC

1.1

ClinPred

0.99

GERP RS

5.0

Varity_R

0.65

gMVP

0.69

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over