dbSNP rs887727938: COX20:c.-10A>T (chr1-244835705-A-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_198076.6(COX20):c.-10A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000197 in 1,260,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

COX20
NM_198076.6 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.20

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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-244835705-A-T is Benign according to our data. Variant chr1-244835705-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 379647.Status of the report is criteria_provided_single_submitter, 1 stars.

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	Effect	Exon Rank	Protein	UniProt
COX20	NM_198076.6	MANE Select	c.-10A>T	5_prime_UTR	Exon 1 of 4	NP_932342.1	Q5RI15-1
COX20	NM_001312872.1		c.-10A>T	5_prime_UTR	Exon 1 of 5	NP_001299801.1	B3KM21
COX20	NM_001312871.1		c.-10A>T	5_prime_UTR	Exon 2 of 5	NP_001299800.1	Q5RI15-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COX20	ENST00000411948.7	TSL:1 MANE Select	c.-10A>T	5_prime_UTR	Exon 1 of 4	ENSP00000406327.2	Q5RI15-1
COX20	ENST00000391839.6	TSL:1	n.50A>T	non_coding_transcript_exon	Exon 1 of 3
COX20	ENST00000366528.3	TSL:2	c.-10A>T	5_prime_UTR	Exon 1 of 5	ENSP00000355486.3	Q5RI15-2

Frequencies

GnomAD3 genomes

AF:

0.0000660

AC:

AN:

151442

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

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:

0.000103

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.00

AC:

AN:

13722

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000215

AC:

238

AN:

1108816

Hom.:

Cov.:

AF XY:

0.000217

AC XY:

115

AN XY:

529578

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23324

American (AMR)

AF:

0.00

AC:

AN:

10366

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15386

East Asian (EAS)

AF:

0.00

AC:

AN:

26696

South Asian (SAS)

AF:

0.00

AC:

AN:

29266

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23794

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3132

European-Non Finnish (NFE)

AF:

0.000255

AC:

238

AN:

932298

Other (OTH)

AF:

0.00

AC:

AN:

44554

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

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

AF:

0.0000660

AC:

AN:

151442

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

73962

show subpopulations

African (AFR)

AF:

0.0000485

AC:

AN:

41196

American (AMR)

AF:

0.00

AC:

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5106

South Asian (SAS)

AF:

0.00

AC:

AN:

4764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10512

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

67864

Other (OTH)

AF:

0.000480

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000712

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.59

PhyloP100

1.2

PromoterAI

-0.051

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over