rs28494975

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-155898234-C-G
• chrX-155898234-C-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_005638.6(VAMP7):​c.327C>G​(p.Val109Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00409 in 1,613,350 control chromosomes in the GnomAD database, including 231 homozygotes. There are 2,722 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (105 hom., 1506 hem., cov: 32)
  • Exomes 𝑓: 0.0022 (126 hom. 1216 hem.)
• Consequence: VAMP7 NM_005638.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant X-155898234-C-G is Benign according to our data. Variant chrX-155898234-C-G is described in ClinVar as Benign. ClinVar VariationId is 777848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.553 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0749 is higher than 0.05.

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>G	p.Val109Val	synonymous	Exon 4 of 8	NP_005629.1	P51809-1
	VAMP7	NM_001185183.2		c.327C>G	p.Val109Val	synonymous	Exon 4 of 7	NP_001172112.1	P51809-2
	VAMP7	NM_001145149.3		c.204C>G	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>G	p.Val109Val	synonymous	Exon 4 of 8	ENSP00000286448.6	P51809-1
	VAMP7	ENST00000262640.11	TSL:1	c.327C>G	p.Val109Val	synonymous	Exon 4 of 7	ENSP00000262640.6	P51809-2
	VAMP7	ENST00000460621.6	TSL:1	c.204C>G	p.Val68Val	synonymous	Exon 3 of 7	ENSP00000427822.1	P51809-3

Frequencies

GnomAD3 genomes AF: 0.0220 AC: 3344 AN: 152018 Hom.: 106 Cov.: 32

Gnomad AFR AF: 0.0770

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00688

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0181

GnomAD2 exomes AF: 0.00556 AC: 1394 AN: 250900 AF XY: 0.00353

Gnomad AFR exome AF: 0.0774

Gnomad AMR exome AF: 0.00318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000618

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00222 AC: 3238 AN: 1461214 Hom.: 126 Cov.: 31 AF XY: 0.00167 AC XY: 1216 AN XY: 726914

African (AFR) AF: 0.0812 AC: 2716 AN: 33444

American (AMR) AF: 0.00331 AC: 148 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5760

European-Non Finnish (NFE) AF: 0.0000522 AC: 58 AN: 1111564

Other (OTH) AF: 0.00472 AC: 285 AN: 60360

GnomAD4 genome AF: 0.0221 AC: 3358 AN: 152136 Hom.: 105 Cov.: 32 AF XY: 0.0202 AC XY: 1506 AN XY: 74378

African (AFR) AF: 0.0771 AC: 3202 AN: 41524

American (AMR) AF: 0.00688 AC: 105 AN: 15272

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4812

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

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67964

Other (OTH) AF: 0.0180 AC: 38 AN: 2116

Bravo AF: 0.0247

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	7.7
DANN	Benign	0.82
PhyloP100		-0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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;