NM_001206641.3:c.47G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001206641.3(COA6):c.47G>C(p.Ser16Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,604,910 control chromosomes in the GnomAD database, including 218,446 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S16I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.60 ( 29116 hom., cov: 34)

Exomes 𝑓: 0.51 ( 189330 hom. )

Consequence

COA6
NM_001206641.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.43

Publications

30 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.4871795E-7).

BP6

Variant 1-234373513-G-C is Benign according to our data. Variant chr1-234373513-G-C is described in ClinVar as Benign. ClinVar VariationId is 380009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206641.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COA6	NM_001206641.3	MANE Select	c.47G>C	p.Ser16Thr	missense	Exon 1 of 3	NP_001193570.2	Q5JTJ3-2
COA6-AS1	NR_125961.1		n.81C>G		non_coding_transcript_exon	Exon 1 of 2
COA6	NM_001012985.2		c.-206G>C		upstream_gene	N/A	NP_001013003.1	Q5JTJ3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COA6	ENST00000366615.10	TSL:1 MANE Select	c.47G>C	p.Ser16Thr	missense	Exon 1 of 3	ENSP00000355574.5	Q5JTJ3-2
COA6	ENST00000619305.1	TSL:1	c.-182G>C		5_prime_UTR	Exon 1 of 3	ENSP00000479686.1	Q5JTJ3-3
COA6-AS1	ENST00000451795.4	TSL:5	n.177C>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.598

AC:

90920

AN:

152106

Hom.:

29060

Cov.:

show subpopulations

Gnomad AFR

AF:

0.835

Gnomad AMI

AF:

0.411

Gnomad AMR

AF:

0.633

Gnomad ASJ

AF:

0.549

Gnomad EAS

AF:

0.484

Gnomad SAS

AF:

0.446

Gnomad FIN

AF:

0.417

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.499

Gnomad OTH

AF:

0.578

GnomAD2 exomes

AF:

0.526

AC:

120956

AN:

229908

AF XY:

0.513

show subpopulations

Gnomad AFR exome

AF:

0.848

Gnomad AMR exome

AF:

0.635

Gnomad ASJ exome

AF:

0.559

Gnomad EAS exome

AF:

0.496

Gnomad FIN exome

AF:

0.422

Gnomad NFE exome

AF:

0.498

Gnomad OTH exome

AF:

0.511

GnomAD4 exome

AF:

0.506

AC:

735150

AN:

1452684

Hom.:

189330

Cov.:

AF XY:

0.503

AC XY:

362967

AN XY:

722014

show subpopulations

African (AFR)

AF:

0.855

AC:

28464

AN:

33272

American (AMR)

AF:

0.633

AC:

27343

AN:

43224

Ashkenazi Jewish (ASJ)

AF:

0.565

AC:

14628

AN:

25880

East Asian (EAS)

AF:

0.427

AC:

16876

AN:

39496

South Asian (SAS)

AF:

0.439

AC:

37654

AN:

85808

European-Finnish (FIN)

AF:

0.432

AC:

22433

AN:

51976

Middle Eastern (MID)

AF:

0.545

AC:

3127

AN:

5740

European-Non Finnish (NFE)

AF:

0.499

AC:

553045

AN:

1107392

Other (OTH)

AF:

0.527

AC:

31580

AN:

59896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

21140

42281

63421

84562

105702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16306

32612

48918

65224

81530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.598

AC:

91023

AN:

152226

Hom.:

29116

Cov.:

AF XY:

0.592

AC XY:

44063

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.835

AC:

34716

AN:

41562

American (AMR)

AF:

0.632

AC:

9671

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.549

AC:

1904

AN:

3468

East Asian (EAS)

AF:

0.485

AC:

2502

AN:

5160

South Asian (SAS)

AF:

0.445

AC:

2149

AN:

4828

European-Finnish (FIN)

AF:

0.417

AC:

4423

AN:

10594

Middle Eastern (MID)

AF:

0.466

AC:

137

AN:

294

European-Non Finnish (NFE)

AF:

0.499

AC:

33939

AN:

67998

Other (OTH)

AF:

0.572

AC:

1207

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1766

3533

5299

7066

8832

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

732

1464

2196

2928

3660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.533

Hom.:

7216

Bravo

AF:

0.627

TwinsUK

AF:

0.508

AC:

1884

ALSPAC

AF:

0.492

AC:

1896

ExAC

AF:

0.514

AC:

60149

Asia WGS

AF:

0.483

AC:

1684

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4 (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.20

(source)

DANN

Benign

0.82

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0079

LIST_S2

Benign

0.20

MetaRNN

Benign

8.5e-7

MetaSVM

Benign

-1.0

PhyloP100

-3.4

PROVEAN

Benign

-0.080

REVEL

Benign

0.041

Sift

Uncertain

0.020

Sift4G

Benign

0.11

Vest4

0.032

ClinPred

0.0077

GERP RS

-4.4

PromoterAI

-0.29

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.019

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over