rs149718203

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_078470.6(COX15):​c.452C>T​(p.Ser151Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

COX15
NM_078470.6 missense

Scores

1
6
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.77
Variant links:
Genes affected
COX15 (HGNC:2263): (cytochrome c oxidase assembly homolog COX15) 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 a protein which is not a structural subunit, but may be essential for the biogenesis of COX formation and may function in the hydroxylation of heme O, according to the yeast mutant studies. This protein is predicted to contain 5 transmembrane domains localized in the mitochondrial inner membrane. Alternative splicing of this gene generates two transcript variants diverging in the 3' region. [provided by RefSeq, Jul 2008]
CUTC (HGNC:24271): (cutC copper transporter) Members of the CUT family of copper transporters are associated with copper homeostasis and are involved in the uptake, storage, delivery, and efflux of copper (Gupta et al., 1995 [PubMed 7635807]; Li et al., 2005 [PubMed 16182249]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COX15NM_078470.6 linkc.452C>T p.Ser151Leu missense_variant Exon 4 of 9 ENST00000016171.6 NP_510870.1 Q7KZN9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COX15ENST00000016171.6 linkc.452C>T p.Ser151Leu missense_variant Exon 4 of 9 1 NM_078470.6 ENSP00000016171.6 Q7KZN9-1
COX15ENST00000370483.9 linkc.452C>T p.Ser151Leu missense_variant Exon 4 of 9 1 ENSP00000359514.5 Q7KZN9-2
ENSG00000285932ENST00000649102.1 linkn.396-27C>T intron_variant Intron 3 of 12 ENSP00000497114.1 A0A3B3IRX1
CUTCENST00000493385.5 linkn.309+3988G>A intron_variant Intron 2 of 4 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461880
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Uncertain
0.046
T
BayesDel_noAF
Benign
-0.17
CADD
Benign
22
DANN
Benign
0.78
DEOGEN2
Uncertain
0.64
.;D
Eigen
Benign
-0.20
Eigen_PC
Benign
0.035
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Pathogenic
0.99
D;D
M_CAP
Benign
0.019
T
MetaRNN
Uncertain
0.60
D;D
MetaSVM
Benign
-0.71
T
MutationAssessor
Benign
1.2
L;L
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-0.98
N;N
REVEL
Uncertain
0.30
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0040
B;B
Vest4
0.65
MutPred
0.54
Gain of MoRF binding (P = 0.1289);Gain of MoRF binding (P = 0.1289);
MVP
0.90
MPC
0.10
ClinPred
0.71
D
GERP RS
4.4
Varity_R
0.13
gMVP
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-101486855; API