rs10521253

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000261643.8(COX10):​c.177+391A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.068 in 152,310 control chromosomes in the GnomAD database, including 395 homozygotes. 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: 𝑓 0.068 ( 395 hom., cov: 33)

Consequence

COX10
ENST00000261643.8 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.993
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0726 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COX10NM_001303.4 linkuse as main transcriptc.177+391A>G intron_variant ENST00000261643.8 NP_001294.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COX10ENST00000261643.8 linkuse as main transcriptc.177+391A>G intron_variant 1 NM_001303.4 ENSP00000261643 P1Q12887-1

Frequencies

GnomAD3 genomes
AF:
0.0680
AC:
10347
AN:
152192
Hom.:
395
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0627
Gnomad AMI
AF:
0.0822
Gnomad AMR
AF:
0.0623
Gnomad ASJ
AF:
0.0646
Gnomad EAS
AF:
0.00578
Gnomad SAS
AF:
0.0397
Gnomad FIN
AF:
0.0977
Gnomad MID
AF:
0.0506
Gnomad NFE
AF:
0.0743
Gnomad OTH
AF:
0.0827
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0680
AC:
10352
AN:
152310
Hom.:
395
Cov.:
33
AF XY:
0.0681
AC XY:
5070
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.0627
Gnomad4 AMR
AF:
0.0622
Gnomad4 ASJ
AF:
0.0646
Gnomad4 EAS
AF:
0.00579
Gnomad4 SAS
AF:
0.0393
Gnomad4 FIN
AF:
0.0977
Gnomad4 NFE
AF:
0.0743
Gnomad4 OTH
AF:
0.0818
Alfa
AF:
0.0693
Hom.:
181
Bravo
AF:
0.0663
Asia WGS
AF:
0.0380
AC:
134
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
CADD
Benign
12
DANN
Benign
0.87

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.

Other links and lift over

dbSNP: rs10521253; hg19: chr17-13978164; API