Variant chr12-6464744-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000361716.8(VAMP1):c.*132G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00811 in 1,519,884 control chromosomes in the GnomAD database, including 826 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.042 ( 428 hom., cov: 31)

Exomes 𝑓: 0.0044 ( 398 hom. )

Consequence

VAMP1
ENST00000361716.8 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0230

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 12-6464744-C-T is Benign according to our data. Variant chr12-6464744-C-T is described in ClinVar as [Benign]. Clinvar id is 1267527.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 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.340+146G>A		intron_variant		ENST00000396308.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAMP1	ENST00000396308.4 linkuse as main transcript	c.340+146G>A		intron_variant		2	NM_014231.5	P1	P23763-1

Frequencies

GnomAD3 genomes

AF:

0.0416

AC:

6323

AN:

152004

Hom.:

426

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0162

Gnomad ASJ

AF:

0.00289

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.0205

GnomAD4 exome

AF:

0.00437

AC:

5983

AN:

1367762

Hom.:

398

Cov.:

AF XY:

0.00397

AC XY:

2673

AN XY:

672704

show subpopulations

Gnomad4 AFR exome

AF:

0.149

Gnomad4 AMR exome

AF:

0.00964

Gnomad4 ASJ exome

AF:

0.00325

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000227

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000481

Gnomad4 OTH exome

AF:

0.00937

GnomAD4 genome

AF:

0.0417

AC:

6345

AN:

152122

Hom.:

428

Cov.:

AF XY:

0.0403

AC XY:

2995

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.144

Gnomad4 AMR

AF:

0.0161

Gnomad4 ASJ

AF:

0.00289

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000897

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.00288

Hom.:

Bravo

AF:

0.0478

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.2

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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