Variant chr1-244835741-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_198076.6(COX20):c.27G>C(p.Glu9Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000016 in 1,121,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E9K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

COX20
NM_198076.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.332

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a chain Cytochrome c oxidase assembly protein COX20, mitochondrial (size 116) in uniprot entity COX20_HUMAN there are 6 pathogenic changes around while only 2 benign (75%) in NM_198076.6

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16435617).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX20	NM_198076.6 link	c.27G>C	p.Glu9Asp	missense_variant	1/4	ENST00000411948.7	NP_932342.1	Q5RI15-1B3KM21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COX20	ENST00000411948.7 link	c.27G>C	p.Glu9Asp	missense_variant	1/4	1	NM_198076.6	ENSP00000406327.2	Q5RI15-1
COX20	ENST00000391839.6 link	n.86G>C		non_coding_transcript_exon_variant	1/3	1
COX20	ENST00000366528.3 link	c.27G>C	p.Glu9Asp	missense_variant	1/5	2		ENSP00000355486.3	Q5RI15-2
COX20	ENST00000498262.1 link	n.83G>C		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000160

AC:

AN:

1121938

Hom.:

Cov.:

AF XY:

0.0000242

AC XY:

AN XY:

537370

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:

0.0000392

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.0000221

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Mitochondrial complex 4 deficiency, nuclear type 11

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jan 28, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.086

T;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.39

T;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.11

N;N

REVEL

Benign

0.093

Sift

Benign

0.15

T;T

Sift4G

Benign

0.091

T;T

Polyphen

1.0

D;.

Vest4

0.13

MutPred

0.16

Loss of glycosylation at P7 (P = 0.0804);Loss of glycosylation at P7 (P = 0.0804);

MVP

0.076

MPC

0.22

ClinPred

0.62

GERP RS

0.091

Varity_R

0.058

gMVP

0.10

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