Genetic Variant COX20:p.Glu6Asp (chr1-244835732-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198076.6(COX20):c.18G>C(p.Glu6Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000893 in 1,119,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E6E) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.9e-7 ( 0 hom. )

Consequence

COX20
NM_198076.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.215

Publications

0 publications found

Variant links:

Genes affected

COX20 (HGNC:26970): (cytochrome c oxidase assembly factor COX20) This gene encodes a protein that plays a role in the assembly of cytochrome C oxidase, an important component of the respiratory pathway. It contains two transmembrane helices and localizes to the mitochondrial membrane. Mutations in this gene can cause mitochondrial complex IV deficiency, which results in ataxia and muscle hypotonia. There are multiple pseudogenes for this gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

COX20 Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
mitochondrial complex IV deficiency, nuclear type 11
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
cytochrome-c oxidase deficiency disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

COX20 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16736376).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198076.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COX20	NM_198076.6	MANE Select	c.18G>C	p.Glu6Asp	missense	Exon 1 of 4	NP_932342.1	Q5RI15-1
COX20	NM_001312872.1		c.18G>C	p.Glu6Asp	missense	Exon 1 of 5	NP_001299801.1	B3KM21
COX20	NM_001312871.1		c.18G>C	p.Glu6Asp	missense	Exon 2 of 5	NP_001299800.1	Q5RI15-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COX20	ENST00000411948.7	TSL:1 MANE Select	c.18G>C	p.Glu6Asp	missense	Exon 1 of 4	ENSP00000406327.2	Q5RI15-1
COX20	ENST00000391839.6	TSL:1	n.77G>C		non_coding_transcript_exon	Exon 1 of 3
COX20	ENST00000366528.3	TSL:2	c.18G>C	p.Glu6Asp	missense	Exon 1 of 5	ENSP00000355486.3	Q5RI15-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.93e-7

AC:

AN:

1119916

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

536344

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23634

American (AMR)

AF:

0.00

AC:

AN:

11396

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15788

East Asian (EAS)

AF:

0.00

AC:

AN:

26934

South Asian (SAS)

AF:

0.00

AC:

AN:

30638

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25204

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3520

European-Non Finnish (NFE)

AF:

0.00000107

AC:

AN:

937712

Other (OTH)

AF:

0.00

AC:

AN:

45090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.57

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

-0.21

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.48

REVEL

Benign

0.043

Sift

Uncertain

0.017

Sift4G

Uncertain

0.052

Polyphen

0.97

Vest4

0.12

MutPred

0.21

Loss of glycosylation at P4 (P = 0.082)

MVP

0.12

MPC

0.029

ClinPred

0.47

GERP RS

0.13

PromoterAI

-0.042

Neutral

(source)

Varity_R

0.20

gMVP

0.12

Mutation Taster

=98/2

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over