Variant rs3731828 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003761.5(VAMP8):c.138C>T(p.Asn46Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,603,078 control chromosomes in the GnomAD database, including 61,693 homozygotes. 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: 𝑓 0.30 ( 6887 hom., cov: 32)

Exomes 𝑓: 0.27 ( 54806 hom. )

Consequence

VAMP8
NM_003761.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.69

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 Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP7

Synonymous conserved (PhyloP=1.69 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAMP8	NM_003761.5 linkuse as main transcript	c.138C>T	p.Asn46Asn	synonymous_variant	2/3	ENST00000263864.10	NP_003752.2	Q9BV40
VAMP8	XM_017005170.2 linkuse as main transcript	c.138C>T	p.Asn46Asn	synonymous_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.138C>T	p.Asn46Asn	synonymous_variant	2/3	1	NM_003761.5	ENSP00000263864.5	Q9BV40
VAMP8	ENST00000409760.1 linkuse as main transcript	c.138C>T	p.Asn46Asn	synonymous_variant	2/4	3		ENSP00000387094.1	B8ZZT4
VAMP8	ENST00000432071.1 linkuse as main transcript	c.60C>T	p.Asn20Asn	synonymous_variant	2/3	3		ENSP00000407984.1	C9JXZ5

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

44885

AN:

151848

Hom.:

6875

Cov.:

show subpopulations

Gnomad AFR

AF:

0.364

Gnomad AMI

AF:

0.346

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.326

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.320

Gnomad MID

AF:

0.236

Gnomad NFE

AF:

0.278

Gnomad OTH

AF:

0.272

GnomAD3 exomes

AF:

0.256

AC:

60922

AN:

238188

Hom.:

8122

AF XY:

0.253

AC XY:

32553

AN XY:

128764

show subpopulations

Gnomad AFR exome

AF:

0.362

Gnomad AMR exome

AF:

0.183

Gnomad ASJ exome

AF:

0.234

Gnomad EAS exome

AF:

0.316

Gnomad SAS exome

AF:

0.156

Gnomad FIN exome

AF:

0.304

Gnomad NFE exome

AF:

0.274

Gnomad OTH exome

AF:

0.250

GnomAD4 exome

AF:

0.272

AC:

395057

AN:

1451112

Hom.:

54806

Cov.:

AF XY:

0.269

AC XY:

193975

AN XY:

720456

show subpopulations

Gnomad4 AFR exome

AF:

0.358

Gnomad4 AMR exome

AF:

0.191

Gnomad4 ASJ exome

AF:

0.238

Gnomad4 EAS exome

AF:

0.313

Gnomad4 SAS exome

AF:

0.163

Gnomad4 FIN exome

AF:

0.299

Gnomad4 NFE exome

AF:

0.280

Gnomad4 OTH exome

AF:

0.271

GnomAD4 genome

AF:

0.296

AC:

44921

AN:

151966

Hom.:

6887

Cov.:

AF XY:

0.294

AC XY:

21810

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.364

Gnomad4 AMR

AF:

0.220

Gnomad4 ASJ

AF:

0.220

Gnomad4 EAS

AF:

0.326

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.320

Gnomad4 NFE

AF:

0.278

Gnomad4 OTH

AF:

0.277

Alfa

AF:

0.271

Hom.:

9417

Bravo

AF:

0.295

Asia WGS

AF:

0.279

AC:

968

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over