Genetic Variant VAMP7:p.Arg173Cys (chrX-155939784-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001185183.2(VAMP7):c.517C>T(p.Arg173Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,612,882 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., 3 hem., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. 8 hem. )

Consequence

VAMP7
NM_001185183.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.60

Publications

0 publications found

Variant links:

Genes affected

VAMP7 (HGNC:11486): (vesicle associated membrane protein 7) This gene encodes a transmembrane protein that is a member of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) family. The encoded protein localizes to late endosomes and lysosomes and is involved in the fusion of transport vesicles to their target membranes. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jun 2010]

VAMP7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.018505305).

BP6

Variant X-155939784-C-T is Benign according to our data. Variant chrX-155939784-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2571389.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001185183.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VAMP7	NM_005638.6	MANE Select	c.585C>T	p.Ile195Ile	synonymous	Exon 7 of 8	NP_005629.1	P51809-1
VAMP7	NM_001185183.2		c.517C>T	p.Arg173Cys	missense	Exon 6 of 7	NP_001172112.1	P51809-2
VAMP7	NM_001145149.3		c.462C>T	p.Ile154Ile	synonymous	Exon 6 of 7	NP_001138621.1	P51809-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VAMP7	ENST00000262640.11	TSL:1	c.517C>T	p.Arg173Cys	missense	Exon 6 of 7	ENSP00000262640.6	P51809-2
VAMP7	ENST00000286448.12	TSL:1 MANE Select	c.585C>T	p.Ile195Ile	synonymous	Exon 7 of 8	ENSP00000286448.6	P51809-1
VAMP7	ENST00000460621.6	TSL:1	c.462C>T	p.Ile154Ile	synonymous	Exon 6 of 7	ENSP00000427822.1	P51809-3

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000478

AC:

AN:

251102

AF XY:

0.0000590

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1460626

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726666

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33440

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.000151

AC:

AN:

39688

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000990

AC:

AN:

1110926

Other (OTH)

AF:

0.0000331

AC:

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41552

American (AMR)

AF:

0.000131

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000579

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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

Bravo

AF:

0.000121

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.2

(source)

DANN

Uncertain

0.99

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.59

M_CAP

Benign

0.011

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.98

PhyloP100

-1.6

PrimateAI

Benign

0.20

PROVEAN

Benign

0.77

REVEL

Benign

0.067

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0

MVP

0.67

MPC

0.52

ClinPred

0.22

GERP RS

-1.3

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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