Genetic Variant NM_004781.4:c.73-561A>C (chr1-7776599-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004781.4(VAMP3):c.73-561A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,164 control chromosomes in the GnomAD database, including 10,320 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 0.35 ( 10311 hom., cov: 32)

Exomes 𝑓: 0.36 ( 9 hom. )

Consequence

VAMP3
NM_004781.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.01

Publications

14 publications found

Variant links:

Genes affected

VAMP3 (HGNC:12644): (vesicle associated membrane protein 3) 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 synaptic vesicles with the presynaptic membrane. This gene is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. Because of its high homology to other known VAMPs, its broad tissue distribution, and its subcellular localization, the protein encoded by this gene was shown to be the human equivalent of the rodent cellubrevin. In platelets the protein resides on a compartment that is not mobilized to the plasma membrane on calcium or thrombin stimulation. [provided by RefSeq, Jul 2008]

VAMP3 links:

ENSG00000269925 (HGNC:):

ENSG00000269925 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAMP3	NM_004781.4 link	c.73-561A>C		intron_variant	Intron 2 of 4	ENST00000054666.11	NP_004772.1	Q15836Q6FGG2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
VAMP3	ENST00000054666.11 link	c.73-561A>C	intron_variant	Intron 2 of 4	1	NM_004781.4	ENSP00000054666.6	Q15836
ENSG00000269925	ENST00000602406.1 link	n.217A>C	non_coding_transcript_exon_variant	Exon 1 of 1	6
VAMP3	ENST00000470357.1 link	c.-12-561A>C	intron_variant	Intron 2 of 4	3		ENSP00000465820.1	K7EKX0

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

53320

AN:

151966

Hom.:

10301

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.315

Gnomad AMR

AF:

0.348

Gnomad ASJ

AF:

0.432

Gnomad EAS

AF:

0.249

Gnomad SAS

AF:

0.450

Gnomad FIN

AF:

0.509

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.369

GnomAD4 exome

AF:

0.362

AC:

AN:

Hom.:

Cov.:

AF XY:

0.545

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.333

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.333

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.393

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.543

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.351

AC:

53369

AN:

152084

Hom.:

10311

Cov.:

AF XY:

0.356

AC XY:

26469

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.192

AC:

7954

AN:

41520

American (AMR)

AF:

0.348

AC:

5311

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.432

AC:

1498

AN:

3470

East Asian (EAS)

AF:

0.249

AC:

1283

AN:

5146

South Asian (SAS)

AF:

0.451

AC:

2172

AN:

4816

European-Finnish (FIN)

AF:

0.509

AC:

5367

AN:

10554

Middle Eastern (MID)

AF:

0.364

AC:

107

AN:

294

European-Non Finnish (NFE)

AF:

0.421

AC:

28601

AN:

67980

Other (OTH)

AF:

0.374

AC:

789

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1702

3405

5107

6810

8512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.347

Hom.:

3344

Bravo

AF:

0.329

Asia WGS

AF:

0.319

AC:

1110

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.0

(source)

DANN

Benign

0.79

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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NM_004781.4:c.73-561A>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over