VAMP1 p.Arg115Gln

Variant names:

• chr12-6462966-CT-TG
• NM_014231.5:c.*1503_*1504delAGinsCA

Your query was ambiguous. Multiple possible variants found:

• chr12-6462966-CT-TG
• chr12-6462965-TCT-CTG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001297438.2(VAMP1):​c.343_344delAGinsCA​(p.Arg115Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: VAMP1 NM_001297438.2 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297438.2. 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.*1503_*1504delAGinsCA		3_prime_UTR	Exon 5 of 5	NP_055046.1	P23763-1
	VAMP1	NM_001297438.2		c.343_344delAGinsCA	p.Arg115Gln	missense splice_region	N/A	NP_001284367.1	F5GZV7
	VAMP1	NM_199245.3		c.*1909_*1910delAGinsCA		3_prime_UTR	Exon 4 of 4	NP_954740.1	P23763-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAMP1	ENST00000396308.4	TSL:2 MANE Select	c.*1503_*1504delAGinsCA		3_prime_UTR	Exon 5 of 5	ENSP00000379602.3	P23763-1
	VAMP1	ENST00000361716.8	TSL:1	c.*1909_*1910delAGinsCA		3_prime_UTR	Exon 4 of 4	ENSP00000355122.3	P23763-3
	VAMP1	ENST00000400911.7	TSL:1	c.341-125_341-124delAGinsCA		intron	N/A	ENSP00000383702.3	P23763-2

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-6572132;