chr17-43015940-C-A

Variant names:

• chr17-43015940-C-A
• rs455055
• NM_006373.4:c.*121G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006373.4(VAT1):​c.*121G>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 0.693 in 1,131,006 control chromosomes in the GnomAD database, including 277,924 homozygotes. 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: 𝑓 0.61 (30274 hom., cov: 27)
  • Exomes 𝑓: 0.71 (247650 hom.)
• Consequence: VAT1 NM_006373.4 3_prime_UTR
• Scores: Splicing: ADA: 0.007101
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.706
• Publications: 31 publications found

Genes affected

VAT1 (HGNC:16919): (vesicle amine transport 1) Synaptic vesicles are responsible for regulating the storage and release of neurotransmitters in the nerve terminal. The protein encoded by this gene is an abundant integral membrane protein of cholinergic synaptic vesicles and is thought to be involved in vesicular transport. It belongs to the quinone oxidoreductase subfamily of zinc-containing alcohol dehydrogenase proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAT1	NM_006373.4	c.*121G>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000355653.8	NP_006364.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAT1	ENST00000355653.8	c.*121G>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_006373.4	ENSP00000347872.2

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92138 AN: 151070 Hom.: 30259 Cov.: 27

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.655

GnomAD4 exome AF: 0.706 AC: 691495 AN: 979818 Hom.: 247650 Cov.: 13 AF XY: 0.705 AC XY: 352827 AN XY: 500234

African (AFR) AF: 0.339 AC: 7979 AN: 23566

American (AMR) AF: 0.801 AC: 29552 AN: 36890

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 12710 AN: 19106

East Asian (EAS) AF: 0.927 AC: 34735 AN: 37452

South Asian (SAS) AF: 0.663 AC: 44516 AN: 67124

European-Finnish (FIN) AF: 0.649 AC: 32639 AN: 50274

Middle Eastern (MID) AF: 0.651 AC: 3007 AN: 4620

European-Non Finnish (NFE) AF: 0.712 AC: 496005 AN: 697016

Other (OTH) AF: 0.693 AC: 30352 AN: 43770

GnomAD4 genome AF: 0.610 AC: 92179 AN: 151188 Hom.: 30274 Cov.: 27 AF XY: 0.613 AC XY: 45207 AN XY: 73800

African (AFR) AF: 0.351 AC: 14453 AN: 41170

American (AMR) AF: 0.727 AC: 11073 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2327 AN: 3460

East Asian (EAS) AF: 0.917 AC: 4668 AN: 5092

South Asian (SAS) AF: 0.675 AC: 3207 AN: 4748

European-Finnish (FIN) AF: 0.630 AC: 6601 AN: 10486

Middle Eastern (MID) AF: 0.596 AC: 174 AN: 292

European-Non Finnish (NFE) AF: 0.704 AC: 47675 AN: 67708

Other (OTH) AF: 0.651 AC: 1371 AN: 2106

Alfa AF: 0.682 Hom.: 41529

Bravo AF: 0.609

Asia WGS AF: 0.730 AC: 2533 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.78
PhyloP100		0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0071
dbscSNV1_RF	Benign	0.014
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: rs455055; hg19: chr17-41167957; COSMIC: COSV99887740; COSMIC: COSV99887740;