chr17-43015940-C-T

Position:

• chr17-43015940-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006373.4(VAT1):​c.*121G>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 0.00000353 in 1,132,796 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: 𝑓 0.000013 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0000020 (0 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151234 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000486

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000204 AC: 2 AN: 981562 Hom.: 0 Cov.: 13 AF XY: 0.00000399 AC XY: 2 AN XY: 501078

Gnomad4 AFR exome AF: 0.0000424

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000228

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151234 Hom.: 0 Cov.: 27 AF XY: 0.0000271 AC XY: 2 AN XY: 73758

Gnomad4 AFR AF: 0.0000486

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Benign	0.79
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	0.016
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;