rs9915302

Variant summary

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

The NM_001303.4(COX10):​c.499+8509T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,176 control chromosomes in the GnomAD database, including 1,953 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 0.15 ( 1953 hom., cov: 33)

Consequence

COX10
NM_001303.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0340
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=-0.9).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COX10NM_001303.4 linkuse as main transcriptc.499+8509T>G intron_variant ENST00000261643.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COX10ENST00000261643.8 linkuse as main transcriptc.499+8509T>G intron_variant 1 NM_001303.4 P1Q12887-1

Frequencies

GnomAD3 genomes
AF:
0.153
AC:
23226
AN:
152058
Hom.:
1952
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0926
Gnomad AMI
AF:
0.164
Gnomad AMR
AF:
0.144
Gnomad ASJ
AF:
0.117
Gnomad EAS
AF:
0.112
Gnomad SAS
AF:
0.151
Gnomad FIN
AF:
0.191
Gnomad MID
AF:
0.120
Gnomad NFE
AF:
0.190
Gnomad OTH
AF:
0.164
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.153
AC:
23235
AN:
152176
Hom.:
1953
Cov.:
33
AF XY:
0.154
AC XY:
11454
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.0925
Gnomad4 AMR
AF:
0.145
Gnomad4 ASJ
AF:
0.117
Gnomad4 EAS
AF:
0.111
Gnomad4 SAS
AF:
0.152
Gnomad4 FIN
AF:
0.191
Gnomad4 NFE
AF:
0.190
Gnomad4 OTH
AF:
0.165
Alfa
AF:
0.174
Hom.:
295
Bravo
AF:
0.148
Asia WGS
AF:
0.136
AC:
468
AN:
3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
1.6
DANN
Benign
0.30

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: rs9915302; hg19: chr17-13988882; API