X-155898234-C-T

Variant names:

• chrX-155898234-C-T
• rs28494975
• NM_005638.6:c.327C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_005638.6(VAMP7):​c.327C>T​(p.Val109Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,022 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V109V) has been classified as Benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., 0 hem., cov: 32)
• Consequence: VAMP7 NM_005638.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.553
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=-0.553 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005638.6. 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.327C>T	p.Val109Val	synonymous	Exon 4 of 8	NP_005629.1	P51809-1
	VAMP7	NM_001185183.2		c.327C>T	p.Val109Val	synonymous	Exon 4 of 7	NP_001172112.1	P51809-2
	VAMP7	NM_001145149.3		c.204C>T	p.Val68Val	synonymous	Exon 3 of 7	NP_001138621.1	P51809-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAMP7	ENST00000286448.12	TSL:1 MANE Select	c.327C>T	p.Val109Val	synonymous	Exon 4 of 8	ENSP00000286448.6	P51809-1
	VAMP7	ENST00000262640.11	TSL:1	c.327C>T	p.Val109Val	synonymous	Exon 4 of 7	ENSP00000262640.6	P51809-2
	VAMP7	ENST00000460621.6	TSL:1	c.204C>T	p.Val68Val	synonymous	Exon 3 of 7	ENSP00000427822.1	P51809-3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152022 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152022 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74254

African (AFR) AF: 0.00 AC: 0 AN: 41406

American (AMR) AF: 0.00 AC: 0 AN: 15252

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67972

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	7.6
DANN	Benign	0.75
PhyloP100		-0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs28494975; hg19: chrX-155127898;