Variant chr12-6462882-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014231.5(VAMP1):c.*1588T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 1,595,188 control chromosomes in the GnomAD database, including 402,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 37884 hom., cov: 33)

Exomes 𝑓: 0.71 ( 364987 hom. )

Consequence

VAMP1
NM_014231.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0740

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 12-6462882-A-G is Benign according to our data. Variant chr12-6462882-A-G is described in ClinVar as [Benign]. Clinvar id is 1234868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.768 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.*1588T>C		3_prime_UTR_variant	5/5	ENST00000396308.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VAMP1	ENST00000396308.4 linkuse as main transcript	c.*1588T>C		3_prime_UTR_variant	5/5	2	NM_014231.5	P1	P23763-1

Frequencies

GnomAD3 genomes

AF:

0.704

AC:

107072

AN:

152040

Hom.:

37845

Cov.:

show subpopulations

Gnomad AFR

AF:

0.719

Gnomad AMI

AF:

0.647

Gnomad AMR

AF:

0.652

Gnomad ASJ

AF:

0.573

Gnomad EAS

AF:

0.777

Gnomad SAS

AF:

0.790

Gnomad FIN

AF:

0.707

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.704

Gnomad OTH

AF:

0.656

GnomAD3 exomes

AF:

0.692

AC:

151463

AN:

219004

Hom.:

52706

AF XY:

0.697

AC XY:

82255

AN XY:

118068

show subpopulations

Gnomad AFR exome

AF:

0.710

Gnomad AMR exome

AF:

0.587

Gnomad ASJ exome

AF:

0.576

Gnomad EAS exome

AF:

0.769

Gnomad SAS exome

AF:

0.789

Gnomad FIN exome

AF:

0.708

Gnomad NFE exome

AF:

0.692

Gnomad OTH exome

AF:

0.668

GnomAD4 exome

AF:

0.710

AC:

1024573

AN:

1443030

Hom.:

364987

Cov.:

AF XY:

0.711

AC XY:

509193

AN XY:

715800

show subpopulations

Gnomad4 AFR exome

AF:

0.715

Gnomad4 AMR exome

AF:

0.593

Gnomad4 ASJ exome

AF:

0.571

Gnomad4 EAS exome

AF:

0.784

Gnomad4 SAS exome

AF:

0.786

Gnomad4 FIN exome

AF:

0.707

Gnomad4 NFE exome

AF:

0.711

Gnomad4 OTH exome

AF:

0.695

GnomAD4 genome

AF:

0.704

AC:

107161

AN:

152158

Hom.:

37884

Cov.:

AF XY:

0.704

AC XY:

52387

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.720

Gnomad4 AMR

AF:

0.652

Gnomad4 ASJ

AF:

0.573

Gnomad4 EAS

AF:

0.777

Gnomad4 SAS

AF:

0.788

Gnomad4 FIN

AF:

0.707

Gnomad4 NFE

AF:

0.704

Gnomad4 OTH

AF:

0.660

Alfa

AF:

0.686

Hom.:

36929

Bravo

AF:

0.694

Asia WGS

AF:

0.761

AC:

2644

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Spastic ataxia 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Myasthenic syndrome, congenital, 25, presynaptic

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

8.3

DANN

Benign

0.72

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