rs10206961

Positions:

• chr2-85587861-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006634.3(VAMP5):​c.3+3368C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,026 control chromosomes in the GnomAD database, including 23,718 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 0.52 (23718 hom., cov: 32)
• Consequence: VAMP5 NM_006634.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

Genes affected

VAMP5 (HGNC:12646): (vesicle associated membrane protein 5) Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein are the main components of a protein complex involved in the docking and/or fusion of vesicles and cell membranes. The VAMP5 gene is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family and the SNARE superfamily. This VAMP family member may participate in vesicle trafficking events that are associated with myogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAMP5	NM_006634.3	c.3+3368C>T		intron_variant		ENST00000306384.5	NP_006625.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAMP5	ENST00000306384.5	c.3+3368C>T		intron_variant		1	NM_006634.3	ENSP00000305647.4

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79347 AN: 151908 Hom.: 23673 Cov.: 32

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.487

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.523 AC: 79446 AN: 152026 Hom.: 23718 Cov.: 32 AF XY: 0.517 AC XY: 38394 AN XY: 74300

Gnomad4 AFR AF: 0.834

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.486

Alfa AF: 0.428 Hom.: 21268

Bravo AF: 0.536

Asia WGS AF: 0.422 AC: 1469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.24
DANN	Benign	0.77

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: rs10206961; hg19: chr2-85814984;