chr5-133980801-G-A

Position:

• chr5-133980801-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003374.3(VDAC1):​c.479C>T​(p.Ala160Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 29)
• Consequence: VDAC1 NM_003374.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.86

Genes affected

VDAC1 (HGNC:12669): (voltage dependent anion channel 1) This gene encodes a voltage-dependent anion channel protein that is a major component of the outer mitochondrial membrane. The encoded protein facilitates the exchange of metabolites and ions across the outer mitochondrial membrane and may regulate mitochondrial functions. This protein also forms channels in the plasma membrane and may be involved in transmembrane electron transport. Alternate splicing results in multiple transcript variants. Multiple pseudogenes of this gene are found on chromosomes 1, 2 3, 6, 9, 12, X and Y.[provided by RefSeq, Sep 2010]

VDAC1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28093898).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VDAC1	NM_003374.3	c.479C>T	p.Ala160Val	missense_variant	6/9	ENST00000265333.8	NP_003365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VDAC1	ENST00000265333.8	c.479C>T	p.Ala160Val	missense_variant	6/9	2	NM_003374.3	ENSP00000265333.3

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2024

The c.479C>T (p.A160V) alteration is located in exon 6 (coding exon 5) of the VDAC1 gene. This alteration results from a C to T substitution at nucleotide position 479, causing the alanine (A) at amino acid position 160 to be replaced by a valine (V). 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	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T;T;T;.
Eigen	Benign	0.039
Eigen_PC	Benign	0.14
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.81	.;.;T;T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.3	M;M;M;.
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-2.1	N;N;N;N
REVEL	Benign	0.087
Sift	Benign	0.054	T;T;T;T
Sift4G	Uncertain	0.037	D;D;D;.
Polyphen		0.0080	B;B;B;.
Vest4		0.28
MutPred		0.46		Loss of ubiquitination at K161 (P = 0.0504);Loss of ubiquitination at K161 (P = 0.0504);Loss of ubiquitination at K161 (P = 0.0504);Loss of ubiquitination at K161 (P = 0.0504);
MVP		0.34
MPC		0.61
ClinPred		0.90	D
GERP RS		5.1
Varity_R		0.27
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-133316492;