Variant 2-85579124-A-T 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.119A>T(p.Asn40Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,456,458 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

VAMP8
NM_003761.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.70

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:

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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
VAMP8	NM_003761.5 linkuse as main transcript	c.119A>T	p.Asn40Ile	missense_variant	2/3	ENST00000263864.10	NP_003752.2	Q9BV40
VAMP8	XM_017005170.2 linkuse as main transcript	c.119A>T	p.Asn40Ile	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.119A>T	p.Asn40Ile	missense_variant	2/3	1	NM_003761.5	ENSP00000263864.5	Q9BV40
VAMP8	ENST00000409760.1 linkuse as main transcript	c.119A>T	p.Asn40Ile	missense_variant	2/4	3		ENSP00000387094.1	B8ZZT4
VAMP8	ENST00000432071.1 linkuse as main transcript	c.41A>T	p.Asn14Ile	missense_variant	2/3	3		ENSP00000407984.1	C9JXZ5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000827

AC:

AN:

241806

Hom.:

AF XY:

0.0000153

AC XY:

AN XY:

130712

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000592

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

AF:

0.00000343

AC:

AN:

1456458

Hom.:

Cov.:

AF XY:

0.00000691

AC XY:

AN XY:

723798

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000453

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:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Jul 31, 2023

The c.119A>T (p.N40I) alteration is located in exon 2 (coding exon 2) of the VAMP8 gene. This alteration results from a A to T substitution at nucleotide position 119, causing the asparagine (N) at amino acid position 40 to be replaced by an isoleucine (I). 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

0.80

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.081

T;T;.

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Benign

0.045

MetaRNN

Uncertain

0.70

D;D;D

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.0

.;M;.

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-4.5

D;D;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.0080

D;D;D

Sift4G

Uncertain

0.013

D;D;T

Polyphen

1.0

.;D;.

Vest4

0.60

MutPred

0.52

.;Loss of disorder (P = 0.0144);Loss of disorder (P = 0.0144);

MVP

0.36

MPC

0.79

ClinPred

0.97

GERP RS

5.7

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.77

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