Variant 8-42405443-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005662.7(VDAC3):c.833G>A(p.Gly278Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

VDAC3
NM_005662.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.86

Variant links:

Genes affected

VDAC3 (HGNC:12674): (voltage dependent anion channel 3) This gene encodes a voltage-dependent anion channel (VDAC), and belongs to the mitochondrial porin family. VDACs are small, integral membrane proteins that traverse the outer mitochondrial membrane and conduct ATP and other small metabolites. They are known to bind several kinases of intermediary metabolism, thought to be involved in translocation of adenine nucleotides, and are hypothesized to form part of the mitochondrial permeability transition pore, which results in the release of cytochrome c at the onset of apoptotic cell death. Alternatively transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Oct 2011]

VDAC3 links:

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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/exons	MANE	Protein	UniProt
VDAC3	NM_005662.7 linkuse as main transcript	c.833G>A	p.Gly278Glu	missense_variant	10/10	ENST00000022615.9	NP_005653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VDAC3	ENST00000022615.9 linkuse as main transcript	c.833G>A	p.Gly278Glu	missense_variant	10/10	1	NM_005662.7	ENSP00000022615	P4	Q9Y277-1
VDAC3	ENST00000521158.5 linkuse as main transcript	c.836G>A	p.Gly279Glu	missense_variant	11/11	5		ENSP00000428845	A1	Q9Y277-2
VDAC3	ENST00000522572.5 linkuse as main transcript	c.386G>A	p.Gly129Glu	missense_variant	9/9	5		ENSP00000428029
VDAC3	ENST00000524291.1 linkuse as main transcript			downstream_gene_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251374

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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

Cov.:

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

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

Jun 18, 2024

The c.836G>A (p.G279E) alteration is located in exon 11 (coding exon 9) of the VDAC3 gene. This alteration results from a G to A substitution at nucleotide position 836, causing the glycine (G) at amino acid position 279 to be replaced by a glutamic acid (E). 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

Pathogenic

0.95

BayesDel_addAF

Uncertain

0.073

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.68

.;.;D

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.38

T;D;D

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.71

D;D;D

MetaSVM

Uncertain

-0.27

MutationAssessor

Uncertain

2.8

.;.;M

MutationTaster

Benign

1.0

D;D;D;N

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

1.8

N;D;D

REVEL

Uncertain

0.34

Sift

Benign

0.062

T;D;D

Sift4G

Benign

0.068

T;D;D

Polyphen

1.0

.;.;D

Vest4

0.68

MutPred

0.46

.;.;Gain of catalytic residue at G278 (P = 0.0714);

MVP

0.16

MPC

0.88

ClinPred

0.86

GERP RS

5.7

Varity_R

0.83

gMVP

0.91

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