Variant 1-244836499-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_198076.6(COX20):c.42+743G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,550,450 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 11 hom. )

Consequence

COX20
NM_198076.6 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.670

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-244836499-G-C is Benign according to our data. Variant chr1-244836499-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1298469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-244836499-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00179 (273/152248) while in subpopulation AMR AF= 0.00628 (96/15282). AF 95% confidence interval is 0.00527. There are 0 homozygotes in gnomad4. There are 155 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COX20	NM_198076.6 linkuse as main transcript	c.42+743G>C		intron_variant		ENST00000411948.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COX20	ENST00000411948.7 linkuse as main transcript	c.42+743G>C		intron_variant		1	NM_198076.6	P1	Q5RI15-1
COX20	ENST00000391839.6 linkuse as main transcript	n.101+743G>C		intron_variant, non_coding_transcript_variant		1
COX20	ENST00000366528.3 linkuse as main transcript	c.57G>C	p.Ser19=	synonymous_variant	2/5	2			Q5RI15-2
COX20	ENST00000498262.1 linkuse as main transcript	n.98+743G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00179

AC:

273

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00629

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00210

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00144

AC:

216

AN:

149980

Hom.:

AF XY:

0.00154

AC XY:

124

AN XY:

80622

show subpopulations

Gnomad AFR exome

AF:

0.000293

Gnomad AMR exome

AF:

0.00293

Gnomad ASJ exome

AF:

0.00107

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000444

Gnomad FIN exome

AF:

0.000770

Gnomad NFE exome

AF:

0.00191

Gnomad OTH exome

AF:

0.00298

GnomAD4 exome

AF:

0.00182

AC:

2539

AN:

1398202

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

1263

AN XY:

689644

show subpopulations

Gnomad4 AFR exome

AF:

0.000222

Gnomad4 AMR exome

AF:

0.00238

Gnomad4 ASJ exome

AF:

0.00103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000757

Gnomad4 FIN exome

AF:

0.000871

Gnomad4 NFE exome

AF:

0.00209

Gnomad4 OTH exome

AF:

0.00174

GnomAD4 genome

AF:

0.00179

AC:

273

AN:

152248

Hom.:

Cov.:

AF XY:

0.00208

AC XY:

155

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00628

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00210

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00156

Hom.:

Bravo

AF:

0.00189

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	COX20: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.84

DANN

Benign

0.46

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