ENST00000361716.8:c.*372C>T

Variant names:

• chr12-6464504-G-A
• rs1949954642
• ENST00000361716.8:c.*372C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000361716.8(VAMP1):​c.*372C>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 0.000000742 in 1,348,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: VAMP1 ENST00000361716.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAMP1	NM_014231.5	c.341-18C>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.341-18C>T		intron_variant	Intron 4 of 4	2	NM_014231.5	ENSP00000379602.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.42e-7 AC: 1 AN: 1348140 Hom.: 0 Cov.: 34 AF XY: 0.00000152 AC XY: 1 AN XY: 659698

African (AFR) AF: 0.00 AC: 0 AN: 29572

American (AMR) AF: 0.00 AC: 0 AN: 27116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21204

East Asian (EAS) AF: 0.00 AC: 0 AN: 35580

South Asian (SAS) AF: 0.00 AC: 0 AN: 69362

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47672

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5396

European-Non Finnish (NFE) AF: 9.47e-7 AC: 1 AN: 1056464

Other (OTH) AF: 0.00 AC: 0 AN: 55774

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	16
DANN	Benign	0.87
PhyloP100		1.9
La Branchor		0.32
BranchPoint Hunter		3.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs1949954642; hg19: chr12-6573670; COSMIC: COSV99869064; COSMIC: COSV99869064;