Genetic Variant VAMP1:p.Arg115Pro (chr12-6462839-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016830.4(VAMP1):c.344G>C(p.Arg115Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R115W) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

VAMP1
NM_016830.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.77

Publications

0 publications found

Variant links:

Genes affected

VAMP1 (HGNC:12642): (vesicle associated membrane protein 1) Synapotobrevins, syntaxins, and the synaptosomal-associated protein SNAP25 are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. The protein encoded by this gene is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. Mutations in this gene are associated with autosomal dominant spastic ataxia 1. Multiple alternative splice variants have been described, but the full-length nature of some variants has not been defined. [provided by RefSeq, Jul 2014]

VAMP1 links:

TAPBPL (HGNC:30683): (TAP binding protein like) Tapasin, or TAPBP (MIM 601962), is a member of the variable-constant Ig superfamily that links major histocompatibility complex (MHC) class I molecules to the transporter associated with antigen processing (TAP; see MIM 170260) in the endoplasmic reticulum (ER). The TAPBP gene is located near the MHC complex on chromosome 6p21.3. TAPBPL is a member of the Ig superfamily that is localized on chromosome 12p13.3, a region somewhat paralogous to the MHC.[supplied by OMIM, Mar 2008]

TAPBPL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055854052).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016830.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VAMP1	NM_014231.5	MANE Select	c.*1631G>C		3_prime_UTR	Exon 5 of 5	NP_055046.1	P23763-1
VAMP1	NM_016830.4		c.344G>C	p.Arg115Pro	missense	Exon 5 of 5	NP_058439.1	P23763-2
VAMP1	NM_199245.3		c.*2037G>C		3_prime_UTR	Exon 4 of 4	NP_954740.1	P23763-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VAMP1	ENST00000400911.7	TSL:1	c.344G>C	p.Arg115Pro	missense	Exon 5 of 5	ENSP00000383702.3	P23763-2
VAMP1	ENST00000396308.4	TSL:2 MANE Select	c.*1631G>C		3_prime_UTR	Exon 5 of 5	ENSP00000379602.3	P23763-1
VAMP1	ENST00000361716.8	TSL:1	c.*2037G>C		3_prime_UTR	Exon 4 of 4	ENSP00000355122.3	P23763-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

234684

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

2.9

(source)

DANN

Benign

0.88

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.29

M_CAP

Benign

0.020

MetaRNN

Benign

0.056

MetaSVM

Benign

-1.1

PhyloP100

-1.8

PROVEAN

Benign

-1.2

REVEL

Benign

0.059

Sift

Uncertain

0.021

Polyphen

0.10

Vest4

0.23

MutPred

0.45

Loss of MoRF binding (P = 0.0093)

MVP

0.068

ClinPred

0.12

GERP RS

-6.2

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over