rs138653672

Variant names:

• chrX-155939784-C-A
• rs138653672
• ENST00000262640.11:c.517C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-155939784-C-A
• chrX-155939784-C-G
• chrX-155939784-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001185183.2(VAMP7):​c.517C>A​(p.Arg173Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,612,764 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R173C) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., 1 hem., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom. 1 hem.)
• Consequence: VAMP7 NM_001185183.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.044149548).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAMP7	NM_005638.6	MANE Select	c.585C>A	p.Ile195Ile	synonymous	Exon 7 of 8	NP_005629.1	P51809-1
	VAMP7	NM_001185183.2		c.517C>A	p.Arg173Ser	missense	Exon 6 of 7	NP_001172112.1	P51809-2
	VAMP7	NM_001145149.3		c.462C>A	p.Ile154Ile	synonymous	Exon 6 of 7	NP_001138621.1	P51809-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAMP7	ENST00000262640.11	TSL:1	c.517C>A	p.Arg173Ser	missense	Exon 6 of 7	ENSP00000262640.6	P51809-2
	VAMP7	ENST00000286448.12	TSL:1 MANE Select	c.585C>A	p.Ile195Ile	synonymous	Exon 7 of 8	ENSP00000286448.6	P51809-1
	VAMP7	ENST00000460621.6	TSL:1	c.462C>A	p.Ile154Ile	synonymous	Exon 6 of 7	ENSP00000427822.1	P51809-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251102 AF XY: 0.0000147

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460626 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726666

African (AFR) AF: 0.0000299 AC: 1 AN: 33440

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110926

Other (OTH) AF: 0.00 AC: 0 AN: 60336

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152138 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74302

African (AFR) AF: 0.0000241 AC: 1 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Bravo AF: 0.00000756

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.2
DANN	Benign	0.87
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.99	T
PhyloP100		-1.6
PrimateAI	Benign	0.19	T
PROVEAN	Benign	0.30	N
REVEL	Benign	0.036
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0030	B
MVP		0.42
MPC		0.33
ClinPred		0.39	T
GERP RS		-1.3
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs138653672; hg19: chrX-155169448;