Variant 1-171706406-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000236192.12(VAMP4):c.358A>G(p.Met120Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

VAMP4
ENST00000236192.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

Variant links:

Genes affected

VAMP4 (HGNC:12645): (vesicle associated membrane protein 4) Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein SNAP25 are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. The protein encoded by this gene is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. This protein may play a role in trans-Golgi network-to-endosome transport. [provided by RefSeq, Jul 2008]

VAMP4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12166974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VAMP4	NM_003762.5 linkuse as main transcript	c.358A>G	p.Met120Val	missense_variant	7/8	ENST00000236192.12	NP_003753.2
VAMP4	NM_001185127.2 linkuse as main transcript	c.355A>G	p.Met119Val	missense_variant	7/8		NP_001172056.1
VAMP4	NR_033704.2 linkuse as main transcript	n.563A>G		non_coding_transcript_exon_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAMP4	ENST00000236192.12 linkuse as main transcript	c.358A>G	p.Met120Val	missense_variant	7/8	1	NM_003762.5	ENSP00000236192	P3	O75379-1
VAMP4	ENST00000367740.2 linkuse as main transcript	c.355A>G	p.Met119Val	missense_variant	7/8	1		ENSP00000356714	A1	O75379-2
VAMP4	ENST00000474047.5 linkuse as main transcript	c.358A>G	p.Met120Val	missense_variant, NMD_transcript_variant	7/9	1		ENSP00000435933		O75379-1
VAMP4	ENST00000482519.1 linkuse as main transcript	n.517A>G		non_coding_transcript_exon_variant	7/8	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247444

Hom.:

AF XY:

0.00000747

AC XY:

AN XY:

133860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1456790

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724704

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 01, 2022

The c.358A>G (p.M120V) alteration is located in exon 7 (coding exon 6) of the VAMP4 gene. This alteration results from a A to G substitution at nucleotide position 358, causing the methionine (M) at amino acid position 120 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

0.074

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.61

DEOGEN2

Benign

0.055

T;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.76

.;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.61

N;.

MutationTaster

Benign

0.64

N;N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.45

N;N

REVEL

Benign

0.093

Sift

Benign

0.15

T;T

Sift4G

Benign

0.21

T;T

Polyphen

0.0

B;B

Vest4

0.37

MutPred

0.57

Loss of MoRF binding (P = 0.1035);.;

MVP

0.043

MPC

0.17

ClinPred

0.095

GERP RS

3.4

Varity_R

0.13

gMVP

0.53

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