ENST00000361716.8:c.*325C>T

Variant names:

• chr12-6464551-G-A
• rs74056957
• ENST00000361716.8:c.*325C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The ENST00000361716.8(VAMP1):​c.*325C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00816 in 1,465,522 control chromosomes in the GnomAD database, including 801 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.042 (423 hom., cov: 31)
  • Exomes 𝑓: 0.0043 (378 hom.)
• Consequence: VAMP1 ENST00000361716.8 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.00
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 12-6464551-G-A is Benign according to our data. Variant chr12-6464551-G-A is described in ClinVar as [Benign]. Clinvar id is 1282347.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 rank	MANE	Protein	UniProt
VAMP1	NM_014231.5	c.341-65C>T		intron_variant	Intron 4 of 4	ENST00000396308.4	NP_055046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAMP1	ENST00000396308.4	c.341-65C>T		intron_variant	Intron 4 of 4	2	NM_014231.5	ENSP00000379602.3

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6311 AN: 151956 Hom.: 421 Cov.: 31

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000868

Gnomad OTH AF: 0.0206

GnomAD4 exome AF: 0.00429 AC: 5633 AN: 1313448 Hom.: 378 Cov.: 36 AF XY: 0.00393 AC XY: 2511 AN XY: 638972

African (AFR) AF: 0.149 AC: 4259 AN: 28536

American (AMR) AF: 0.0106 AC: 222 AN: 20974

Ashkenazi Jewish (ASJ) AF: 0.00333 AC: 64 AN: 19212

East Asian (EAS) AF: 0.0000284 AC: 1 AN: 35164

South Asian (SAS) AF: 0.000236 AC: 15 AN: 63510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45876

Middle Eastern (MID) AF: 0.00976 AC: 50 AN: 5124

European-Non Finnish (NFE) AF: 0.000470 AC: 489 AN: 1040818

Other (OTH) AF: 0.00983 AC: 533 AN: 54234

GnomAD4 genome AF: 0.0416 AC: 6332 AN: 152074 Hom.: 423 Cov.: 31 AF XY: 0.0403 AC XY: 2993 AN XY: 74352

African (AFR) AF: 0.144 AC: 5964 AN: 41454

American (AMR) AF: 0.0161 AC: 246 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3468

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000868 AC: 59 AN: 67982

Other (OTH) AF: 0.0208 AC: 44 AN: 2112

Alfa AF: 0.0194 Hom.: 64

Bravo AF: 0.0478

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 25, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	15
DANN	Benign	0.81
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs74056957; hg19: chr12-6573717;