rs17023875

Variant names:

• chr12-95273067-T-C
• rs17023875
• NM_017599.4:c.849-1675T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017599.4(VEZT):​c.849-1675T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,174 control chromosomes in the GnomAD database, including 1,339 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1339 hom., cov: 32)
• Consequence: VEZT NM_017599.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• Publications: 2 publications found

Genes affected

VEZT (HGNC:18258): (vezatin, adherens junctions transmembrane protein) This gene encodes a transmembrane protein which has been localized to adherens junctions and shown to bind to myosin VIIA. Examination of expression of this gene in gastric cancer tissues have shown that expression is decreased which appears to be related to hypermethylation of the promoter. Expression of this gene may also be inhibited by binding of a specific microRNA to a target sequence in the 3' UTR of the transcripts. A pseudogene of this gene is located on the X chromosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017599.4. 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
	VEZT	NM_017599.4	MANE Select	c.849-1675T>C		intron	N/A	NP_060069.3
	VEZT	NM_001352088.2		c.918-1675T>C		intron	N/A	NP_001339017.1
	VEZT	NM_001352089.2		c.861-1675T>C		intron	N/A	NP_001339018.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEZT	ENST00000436874.6	TSL:1 MANE Select	c.849-1675T>C		intron	N/A	ENSP00000410083.1	Q9HBM0-1
	VEZT	ENST00000397792.8	TSL:1	c.717-1675T>C		intron	N/A	ENSP00000380894.4	F8W8C2
	VEZT	ENST00000546398.5	TSL:1	n.901-1675T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16763 AN: 152056 Hom.: 1336 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0668

Gnomad ASJ AF: 0.0582

Gnomad EAS AF: 0.00288

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0686

Gnomad OTH AF: 0.103

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.110 AC: 16781 AN: 152174 Hom.: 1339 Cov.: 32 AF XY: 0.108 AC XY: 8025 AN XY: 74414

African (AFR) AF: 0.230 AC: 9539 AN: 41472

American (AMR) AF: 0.0666 AC: 1019 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0582 AC: 202 AN: 3472

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5188

South Asian (SAS) AF: 0.137 AC: 660 AN: 4818

European-Finnish (FIN) AF: 0.0318 AC: 337 AN: 10610

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0686 AC: 4663 AN: 68012

Other (OTH) AF: 0.102 AC: 216 AN: 2108

Alfa AF: 0.0947 Hom.: 165

Bravo AF: 0.116

Asia WGS AF: 0.0640 AC: 224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.9
DANN	Benign	0.89
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17023875; hg19: chr12-95666843;