rs3731828

chr2-85579143-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003761.5(VAMP8):c.138C>T(p.Asn46=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69

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]

ACMG classification

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	UniProt
VAMP8	NM_003761.5	c.138C>T	p.Asn46=	synonymous_variant	2/3	ENST00000263864.10
VAMP8	XM_017005170.2	c.138C>T	p.Asn46=	synonymous_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAMP8	ENST00000263864.10	c.138C>T	p.Asn46=	synonymous_variant	2/3	1	NM_003761.5	P1
VAMP8	ENST00000409760.1	c.138C>T	p.Asn46=	synonymous_variant	2/4	3
VAMP8	ENST00000432071.1	c.60C>T	p.Asn20=	synonymous_variant	2/3	3

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44885 AN: 151848 Hom.: 6875 Cov.: 32

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

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.: 34 AF XY: 0.269 AC XY: 193975 AN XY: 720456

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.: 32 AF XY: 0.294 AC XY: 21810 AN XY: 74290

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	11
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

Other links and lift over

dbSNP: rs3731828; hg19: chr2-85806266; COSMIC: COSV55705120;