Genetic Variant VAMP8:c.*143T>G (chr2-85581859-T-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003761.5(VAMP8):c.*143T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000395 in 1,138,122 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00041 ( 3 hom. )

Consequence

VAMP8
NM_003761.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0580

Publications

68 publications found

Variant links:

Genes affected

VAMP8 (HGNC:12647): (vesicle associated membrane protein 8) This gene encodes an integral membrane protein that belongs to the synaptobrevin/vesicle-associated membrane protein subfamily of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The encoded protein is involved in the fusion of synaptic vesicles with the presynaptic membrane.[provided by RefSeq, Jun 2010]

VAMP8 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003761.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAMP8	NM_003761.5	MANE Select	c.*143T>G		3_prime_UTR	Exon 3 of 3	NP_003752.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VAMP8	ENST00000263864.10	TSL:1 MANE Select	c.*143T>G	3_prime_UTR	Exon 3 of 3	ENSP00000263864.5	Q9BV40
VAMP8	ENST00000409760.1	TSL:3	c.*279T>G	3_prime_UTR	Exon 4 of 4	ENSP00000387094.1	B8ZZT4
VAMP8	ENST00000432071.1	TSL:3	c.*143T>G	3_prime_UTR	Exon 3 of 3	ENSP00000407984.1	C9JXZ5

Frequencies

GnomAD3 genomes

AF:

0.000323

AC:

AN:

151776

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00542

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000950

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00144

GnomAD4 exome

AF:

0.000406

AC:

400

AN:

986226

Hom.:

Cov.:

AF XY:

0.000405

AC XY:

202

AN XY:

498786

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22706

American (AMR)

AF:

0.00

AC:

AN:

29438

Ashkenazi Jewish (ASJ)

AF:

0.000111

AC:

AN:

17964

East Asian (EAS)

AF:

0.00597

AC:

221

AN:

37042

South Asian (SAS)

AF:

0.000208

AC:

AN:

62600

European-Finnish (FIN)

AF:

0.000359

AC:

AN:

38968

Middle Eastern (MID)

AF:

0.000578

AC:

AN:

3458

European-Non Finnish (NFE)

AF:

0.000181

AC:

132

AN:

729886

Other (OTH)

AF:

0.000362

AC:

AN:

44164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.000323

AC:

AN:

151896

Hom.:

Cov.:

AF XY:

0.000337

AC XY:

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41410

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00543

AC:

AN:

5154

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0000950

AC:

AN:

10530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

67944

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00000845

Hom.:

21461

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.4

(source)

DANN

Benign

0.41

PhyloP100

-0.058

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over