2-85581859-T-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003761.5(VAMP8):c.*143T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000395 in 1,138,122 control chromosomes in the GnomAD database, including 3 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 0.00032 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00041 (3 hom.)
• Consequence: VAMP8 NM_003761.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VAMP8	NM_003761.5	c.*143T>G		3_prime_UTR_variant	3/3	ENST00000263864.10
VAMP8	XM_017005170.2	c.*279T>G		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAMP8	ENST00000263864.10	c.*143T>G		3_prime_UTR_variant	3/3	1	NM_003761.5	P1
VAMP8	ENST00000409760.1	c.*279T>G		3_prime_UTR_variant	4/4	3
VAMP8	ENST00000432071.1	c.*143T>G		3_prime_UTR_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.000323 AC: 49 AN: 151776 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00542

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000950

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00144

GnomAD4 exome AF: 0.000406 AC: 400 AN: 986226 Hom.: 3 Cov.: 13 AF XY: 0.000405 AC XY: 202 AN XY: 498786

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000111

Gnomad4 EAS exome AF: 0.00597

Gnomad4 SAS exome AF: 0.000208

Gnomad4 FIN exome AF: 0.000359

Gnomad4 NFE exome AF: 0.000181

Gnomad4 OTH exome AF: 0.000362

GnomAD4 genome AF: 0.000323 AC: 49 AN: 151896 Hom.: 0 Cov.: 30 AF XY: 0.000337 AC XY: 25 AN XY: 74234

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00543

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.0000950

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.0000124 Hom.: 14248

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.4
Dann	Benign	0.41

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: rs1010; hg19: chr2-85808982;