chr12-6464744-C-T

Variant names:

• chr12-6464744-C-T
• rs71584833
• ENST00000361716.8:c.*132G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_199245.3(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 NM_199245.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0230
• 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199245.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAMP1	NM_014231.5	MANE Select	c.340+146G>A		intron	N/A	NP_055046.1	P23763-1
	VAMP1	NM_199245.3		c.*132G>A		3_prime_UTR	Exon 4 of 4	NP_954740.1	P23763-3
	VAMP1	NM_001297438.2		c.340+146G>A		intron	N/A	NP_001284367.1	F5GZV7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAMP1	ENST00000361716.8	TSL:1	c.*132G>A		3_prime_UTR	Exon 4 of 4	ENSP00000355122.3	P23763-3
	VAMP1	ENST00000396308.4	TSL:2 MANE Select	c.340+146G>A		intron	N/A	ENSP00000379602.3	P23763-1
	VAMP1	ENST00000400911.7	TSL:1	c.340+146G>A		intron	N/A	ENSP00000383702.3	P23763-2

Frequencies

GnomAD3 genomes AF: 0.0416 AC: 6323 AN: 152004 Hom.: 426 Cov.: 31

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.: 32 AF XY: 0.00397 AC XY: 2673 AN XY: 672704

African (AFR) AF: 0.149 AC: 4522 AN: 30330

American (AMR) AF: 0.00964 AC: 286 AN: 29658

Ashkenazi Jewish (ASJ) AF: 0.00325 AC: 66 AN: 20294

East Asian (EAS) AF: 0.00 AC: 0 AN: 38766

South Asian (SAS) AF: 0.000227 AC: 16 AN: 70600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43278

Middle Eastern (MID) AF: 0.00969 AC: 47 AN: 4852

European-Non Finnish (NFE) AF: 0.000481 AC: 516 AN: 1073442

Other (OTH) AF: 0.00937 AC: 530 AN: 56542

GnomAD4 genome AF: 0.0417 AC: 6345 AN: 152122 Hom.: 428 Cov.: 31 AF XY: 0.0403 AC XY: 2995 AN XY: 74364

African (AFR) AF: 0.144 AC: 5975 AN: 41446

American (AMR) AF: 0.0161 AC: 246 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00289 AC: 10 AN: 3466

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5162

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.000897 AC: 61 AN: 68010

Other (OTH) AF: 0.0208 AC: 44 AN: 2116

Alfa AF: 0.0108 Hom.: 35

Bravo AF: 0.0478

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.2
DANN	Benign	0.69
PhyloP100		-0.023
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs71584833; hg19: chr12-6573910; COSMIC: COSV56947035; COSMIC: COSV56947035;