Variant chr2-85579121-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003761.5(VAMP8):c.116A>G(p.Glu39Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000311 in 1,608,018 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

VAMP8
NM_003761.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.44

Variant links:

Genes affected

VAMP8 (HGNC:12647): (vesicle associated membrane protein 8) This gene encodes an integral membrane protein that belongs to the synaptobrevin/vesicle-associated membrane protein subfamily of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The encoded protein is involved in the fusion of synaptic vesicles with the presynaptic membrane.[provided by RefSeq, Jun 2010]

VAMP8 links:

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/exons	MANE	Protein	UniProt
VAMP8	NM_003761.5 linkuse as main transcript	c.116A>G	p.Glu39Gly	missense_variant	2/3	ENST00000263864.10	NP_003752.2	Q9BV40
VAMP8	XM_017005170.2 linkuse as main transcript	c.116A>G	p.Glu39Gly	missense_variant	2/4		XP_016860659.1	B8ZZT4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
VAMP8	ENST00000263864.10 linkuse as main transcript	c.116A>G	p.Glu39Gly	missense_variant	2/3	1	NM_003761.5	ENSP00000263864.5	Q9BV40
VAMP8	ENST00000409760.1 linkuse as main transcript	c.116A>G	p.Glu39Gly	missense_variant	2/4	3		ENSP00000387094.1	B8ZZT4
VAMP8	ENST00000432071.1 linkuse as main transcript	c.38A>G	p.Glu13Gly	missense_variant	2/3	3		ENSP00000407984.1	C9JXZ5

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

151964

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.0000374

AC:

AN:

240790

Hom.:

AF XY:

0.0000307

AC XY:

AN XY:

130130

show subpopulations

Gnomad AFR exome

AF:

0.000332

Gnomad AMR exome

AF:

0.0000594

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000341

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000921

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000165

AC:

AN:

1455936

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

723572

show subpopulations

Gnomad4 AFR exome

AF:

0.000300

Gnomad4 AMR exome

AF:

0.0000908

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000631

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.000171

AC:

AN:

152082

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.0000580

Hom.:

Bravo

AF:

0.000280

ExAC

AF:

0.0000741

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Nov 15, 2023

The c.116A>G (p.E39G) alteration is located in exon 2 (coding exon 2) of the VAMP8 gene. This alteration results from a A to G substitution at nucleotide position 116, causing the glutamic acid (E) at amino acid position 39 to be replaced by a glycine (G). 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

Uncertain

0.48

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.15

T;T;.

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.073

MetaRNN

Uncertain

0.63

D;D;D

MetaSVM

Benign

-0.32

MutationAssessor

Uncertain

2.8

.;M;.

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-6.6

D;D;D

REVEL

Uncertain

0.50

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.73

MVP

0.67

MPC

0.84

ClinPred

0.87

GERP RS

5.7

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.84

gMVP

0.87

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