rs71584837

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_016830.4(VAMP1):c.343C>T(p.Arg115Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00443 in 1,606,292 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0045 ( 19 hom. )

Consequence

VAMP1
NM_016830.4 missense, splice_region

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.347

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025634766).

BP6

Variant 12-6462840-G-A is Benign according to our data. Variant chr12-6462840-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 448851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-6462840-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00373 (568/152316) while in subpopulation NFE AF= 0.00598 (407/68024). AF 95% confidence interval is 0.0055. There are 3 homozygotes in gnomad4. There are 284 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAMP1	NM_014231.5 link	c.*1630C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000396308.4	NP_055046.1	P23763-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAMP1	ENST00000396308 link	c.*1630C>T		3_prime_UTR_variant	Exon 5 of 5	2	NM_014231.5	ENSP00000379602.3		P23763-1

Frequencies

GnomAD3 genomes

AF:

0.00373

AC:

568

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00594

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00598

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00331

AC:

778

AN:

234946

Hom.:

AF XY:

0.00347

AC XY:

442

AN XY:

127222

show subpopulations

Gnomad AFR exome

AF:

0.000633

Gnomad AMR exome

AF:

0.00160

Gnomad ASJ exome

AF:

0.000821

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00192

Gnomad FIN exome

AF:

0.00525

Gnomad NFE exome

AF:

0.00501

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00450

AC:

6545

AN:

1453976

Hom.:

Cov.:

AF XY:

0.00439

AC XY:

3170

AN XY:

722266

show subpopulations

Gnomad4 AFR exome

AF:

0.000839

Gnomad4 AMR exome

AF:

0.00179

Gnomad4 ASJ exome

AF:

0.00100

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00205

Gnomad4 FIN exome

AF:

0.00538

Gnomad4 NFE exome

AF:

0.00518

Gnomad4 OTH exome

AF:

0.00339

GnomAD4 genome

AF:

0.00373

AC:

568

AN:

152316

Hom.:

Cov.:

AF XY:

0.00381

AC XY:

284

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00594

Gnomad4 NFE

AF:

0.00598

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00482

Hom.:

Bravo

AF:

0.00323

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.000766

AC:

ESP6500EA

AF:

0.00530

AC:

ExAC

AF:

0.00351

AC:

424

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

VAMP1: BP4, BS2 -

Dec 19, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.46

M_CAP

Benign

0.025

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.1

PROVEAN

Benign

0.40

REVEL

Benign

0.041

Sift

Uncertain

0.0040

Polyphen

0.0

Vest4

0.10

MVP

0.043

ClinPred

0.021

GERP RS

1.5

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over