Variant chr12-6464550-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000361716.8(VAMP1):c.*326A>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 0.309 in 1,465,846 control chromosomes in the GnomAD database, including 70,526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6221 hom., cov: 31)

Exomes 𝑓: 0.31 ( 64305 hom. )

Consequence

VAMP1
ENST00000361716.8 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.14

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 12-6464550-T-C is Benign according to our data. Variant chr12-6464550-T-C is described in ClinVar as [Benign]. Clinvar id is 1295842.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VAMP1	NM_014231.5 linkuse as main transcript	c.341-64A>G		intron_variant		ENST00000396308.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAMP1	ENST00000396308.4 linkuse as main transcript	c.341-64A>G		intron_variant		2	NM_014231.5	P1	P23763-1

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42630

AN:

151520

Hom.:

6219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.422

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.297

Gnomad EAS

AF:

0.335

Gnomad SAS

AF:

0.354

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.313

Gnomad OTH

AF:

0.273

GnomAD4 exome

AF:

0.312

AC:

409615

AN:

1314208

Hom.:

64305

Cov.:

AF XY:

0.313

AC XY:

200051

AN XY:

639518

show subpopulations

Gnomad4 AFR exome

AF:

0.203

Gnomad4 AMR exome

AF:

0.195

Gnomad4 ASJ exome

AF:

0.298

Gnomad4 EAS exome

AF:

0.346

Gnomad4 SAS exome

AF:

0.347

Gnomad4 FIN exome

AF:

0.328

Gnomad4 NFE exome

AF:

0.314

Gnomad4 OTH exome

AF:

0.305

GnomAD4 genome

AF:

0.281

AC:

42660

AN:

151638

Hom.:

6221

Cov.:

AF XY:

0.283

AC XY:

20977

AN XY:

74080

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.240

Gnomad4 ASJ

AF:

0.297

Gnomad4 EAS

AF:

0.335

Gnomad4 SAS

AF:

0.355

Gnomad4 FIN

AF:

0.339

Gnomad4 NFE

AF:

0.313

Gnomad4 OTH

AF:

0.276

Alfa

AF:

0.292

Hom.:

2857

Bravo

AF:

0.267

Asia WGS

AF:

0.264

AC:

918

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.81

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

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