Genetic Variant NM_006373.4:c.388-665C>T (chr17-43019464-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006373.4(VAT1):c.388-665C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 152,138 control chromosomes in the GnomAD database, including 44,263 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 0.76 ( 44238 hom., cov: 31)

Exomes 𝑓: 0.82 ( 25 hom. )

Consequence

VAT1
NM_006373.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0660

Publications

11 publications found

Variant links:

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]

VAT1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAT1	NM_006373.4 link	c.388-665C>T		intron_variant	Intron 1 of 5	ENST00000355653.8	NP_006364.2	Q99536-1A0A024R1Z6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAT1	ENST00000355653.8 link	c.388-665C>T		intron_variant	Intron 1 of 5	1	NM_006373.4	ENSP00000347872.2		Q99536-1

Frequencies

GnomAD3 genomes

AF:

0.757

AC:

114961

AN:

151946

Hom.:

44221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.612

Gnomad AMI

AF:

0.771

Gnomad AMR

AF:

0.834

Gnomad ASJ

AF:

0.824

Gnomad EAS

AF:

0.914

Gnomad SAS

AF:

0.733

Gnomad FIN

AF:

0.762

Gnomad MID

AF:

0.813

Gnomad NFE

AF:

0.811

Gnomad OTH

AF:

0.787

GnomAD4 exome

AF:

0.824

AC:

AN:

Hom.:

Cov.:

AF XY:

0.765

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.809

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.557

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.756

AC:

115017

AN:

152064

Hom.:

44238

Cov.:

AF XY:

0.757

AC XY:

56243

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.612

AC:

25347

AN:

41446

American (AMR)

AF:

0.835

AC:

12746

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.824

AC:

2857

AN:

3466

East Asian (EAS)

AF:

0.914

AC:

4736

AN:

5180

South Asian (SAS)

AF:

0.732

AC:

3535

AN:

4830

European-Finnish (FIN)

AF:

0.762

AC:

8043

AN:

10562

Middle Eastern (MID)

AF:

0.806

AC:

237

AN:

294

European-Non Finnish (NFE)

AF:

0.811

AC:

55166

AN:

67994

Other (OTH)

AF:

0.781

AC:

1650

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1362

2723

4085

5446

6808

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

846

1692

2538

3384

4230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.803

Hom.:

45518

Bravo

AF:

0.761

Asia WGS

AF:

0.779

AC:

2706

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.4

(source)

DANN

Benign

0.85

PhyloP100

-0.066

PromoterAI

0.018

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over