rs761136486

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_182971.3(COX8C):​c.28G>A​(p.Ala10Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,452,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A10S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

COX8C
NM_182971.3 missense

Scores

1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.55
Variant links:
Genes affected
COX8C (HGNC:24382): (cytochrome c oxidase subunit 8C) Predicted to be involved in mitochondrial electron transport, cytochrome c to oxygen. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]
UNC79 (HGNC:19966): (unc-79 homolog, NALCN channel complex subunit) The NALCN channel is responsible for Na(+) leak currents. The protein encoded by this gene, along with UNC80, is an accessory subunit of the NALCN channel that contributes to the Ca(2+) sensitivity of the channel. [provided by RefSeq, Sep 2016]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.042357534).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COX8CNM_182971.3 linkc.28G>A p.Ala10Thr missense_variant Exon 1 of 2 ENST00000342144.3 NP_892016.1 Q7Z4L0
UNC79NM_020818.5 linkc.-351+13773G>A intron_variant Intron 1 of 49 NP_065869.3 Q9P2D8-2
UNC79XM_011537027.3 linkc.-180+13773G>A intron_variant Intron 1 of 51 XP_011535329.1
UNC79NR_144398.1 linkn.325-732G>A intron_variant Intron 1 of 1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COX8CENST00000342144.3 linkc.28G>A p.Ala10Thr missense_variant Exon 1 of 2 1 NM_182971.3 ENSP00000340568.2 Q7Z4L0
UNC79ENST00000256339.8 linkc.-351+13773G>A intron_variant Intron 1 of 49 5 ENSP00000256339.4 Q9P2D8-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000428
AC:
1
AN:
233660
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
129114
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000294
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS 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:
0.00000413
AC:
6
AN:
1452498
Hom.:
0
Cov.:
31
AF XY:
0.00000415
AC XY:
3
AN XY:
722838
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000225
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000207
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000836
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
0.50
DANN
Benign
0.77
DEOGEN2
Benign
0.063
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.013
N
M_CAP
Benign
0.0026
T
MetaRNN
Benign
0.042
T
MetaSVM
Benign
-1.0
T
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-0.46
N
REVEL
Benign
0.051
Sift
Benign
0.71
T
Sift4G
Benign
0.51
T
Polyphen
0.0
B
Vest4
0.17
MutPred
0.25
Gain of phosphorylation at A10 (P = 0.0019);
MVP
0.014
MPC
0.29
ClinPred
0.057
T
GERP RS
-2.3
Varity_R
0.021
gMVP
0.33

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: rs761136486; hg19: chr14-93813642; API