Variant 14-93347282-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_182971.3(COX8C):c.14G>A(p.Arg5His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,604,594 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

COX8C
NM_182971.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.856

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]

COX8C links:

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]

UNC79 links:

Genome browser will be placed here

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=0.05951628).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
COX8C	NM_182971.3 linkuse as main transcript	c.14G>A	p.Arg5His	missense_variant	1/2	ENST00000342144.3
UNC79	NM_020818.5 linkuse as main transcript	c.-351+13759G>A		intron_variant
UNC79	XM_011537027.3 linkuse as main transcript	c.-180+13759G>A		intron_variant
UNC79	NR_144398.1 linkuse as main transcript	n.325-746G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COX8C	ENST00000342144.3 linkuse as main transcript	c.14G>A	p.Arg5His	missense_variant	1/2	1	NM_182971.3	P1
UNC79	ENST00000256339.8 linkuse as main transcript	c.-351+13759G>A		intron_variant		5			Q9P2D8-2

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000841

AC:

AN:

237734

Hom.:

AF XY:

0.000107

AC XY:

AN XY:

130294

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000591

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:

0.000169

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000108

AC:

157

AN:

1452426

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

722612

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000452

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000133

Gnomad4 OTH exome

AF:

0.0000833

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000663

Hom.:

Bravo

AF:

0.000102

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000350

AC:

ExAC

AF:

0.000108

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.14G>A (p.R5H) alteration is located in exon 1 (coding exon 1) of the COX8C gene. This alteration results from a G to A substitution at nucleotide position 14, causing the arginine (R) at amino acid position 5 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.67

CADD

Benign

3.7

DANN

Benign

0.76

DEOGEN2

Benign

0.082

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.016

M_CAP

Benign

0.0049

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.1

REVEL

Benign

0.029

Sift

Benign

0.15

Sift4G

Benign

0.16

Polyphen

0.89

Vest4

0.13

MVP

0.014

MPC

0.42

ClinPred

0.061

GERP RS

-4.8

Varity_R

0.022

gMVP

0.38

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over