Genetic Variant COX10:c.-109G>C (chr17-14069497-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000429152.6(COX10):c.-109G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000833 in 1,200,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.3e-7 ( 0 hom. )

Consequence

COX10
ENST00000429152.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.55

Publications

0 publications found

Variant links:

Genes affected

COX10 (HGNC:2260): (cytochrome c oxidase assembly factor heme A:farnesyltransferase COX10) Cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. This component is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene encodes heme A:farnesyltransferase, which is not a structural subunit but required for the expression of functional COX and functions in the maturation of the heme A prosthetic group of COX. This protein is predicted to contain 7-9 transmembrane domains localized in the mitochondrial inner membrane. A gene mutation, which results in the substitution of a lysine for an asparagine (N204K), is identified to be responsible for cytochrome c oxidase deficiency. In addition, this gene is disrupted in patients with CMT1A (Charcot-Marie-Tooth type 1A) duplication and with HNPP (hereditary neuropathy with liability to pressure palsies) deletion. [provided by RefSeq, Jul 2008]

COX10 links:

COX10-DT (HGNC:38873): (COX10 divergent transcript)

COX10-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000429152.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COX10	NM_001303.4	MANE Select	c.-109G>C		upstream_gene	N/A	NP_001294.2
	COX10-DT	NR_049718.1		n.-39C>G		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COX10	ENST00000429152.6	TSL:2	c.-109G>C	5_prime_UTR	Exon 1 of 3	ENSP00000397750.2	H7C101
COX10	ENST00000664217.1		n.-109G>C	non_coding_transcript_exon	Exon 1 of 14	ENSP00000499396.1	Q12887-1
COX10	ENST00000670279.1		n.-109G>C	non_coding_transcript_exon	Exon 1 of 11	ENSP00000499450.1	A0A590UJJ5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.33e-7

AC:

AN:

1200294

Hom.:

Cov.:

AF XY:

0.00000165

AC XY:

AN XY:

604706

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28068

American (AMR)

AF:

0.00

AC:

AN:

39022

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23832

East Asian (EAS)

AF:

0.00

AC:

AN:

36384

South Asian (SAS)

AF:

0.00

AC:

AN:

77134

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49364

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3920

European-Non Finnish (NFE)

AF:

0.00000112

AC:

AN:

891242

Other (OTH)

AF:

0.00

AC:

AN:

51328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.049

(source)

DANN

Benign

0.52

PhyloP100

-3.6

PromoterAI

0.070

Neutral

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over