chr17-43015940-C-A

Position:

• chr17-43015940-C-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
VAT1	NM_006373.4	c.*121G>T		3_prime_UTR_variant	6/6	ENST00000355653.8	NP_006364.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAT1	ENST00000355653	c.*121G>T		3_prime_UTR_variant	6/6	1	NM_006373.4	ENSP00000347872.2
VAT1	ENST00000587173	c.*121G>T		3_prime_UTR_variant	6/6	2		ENSP00000465946.1
VAT1	ENST00000420567	c.*121G>T		3_prime_UTR_variant	6/6	2		ENSP00000408553.2
VAT1	ENST00000592388.1	n.*120+1G>T		splice_donor_variant, intron_variant		5		ENSP00000465239.1

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

Gnomad4 AFR exome AF: 0.339

Gnomad4 AMR exome AF: 0.801

Gnomad4 ASJ exome AF: 0.665

Gnomad4 EAS exome AF: 0.927

Gnomad4 SAS exome AF: 0.663

Gnomad4 FIN exome AF: 0.649

Gnomad4 NFE exome AF: 0.712

Gnomad4 OTH exome AF: 0.693

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

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.727

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.917

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.630

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.651

Alfa AF: 0.685 Hom.: 30219

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs455055; hg19: chr17-41167957; COSMIC: COSV99887740; COSMIC: COSV99887740;