12-95302644-A-G

Variant names:

• chr12-95302644-A-G
• rs3596
• NM_017599.4:c.*1971A>G

Variant summary

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

The NM_017599.4(VEZT):​c.*1971A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,874 control chromosomes in the GnomAD database, including 18,154 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 0.48 (18154 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: VEZT NM_017599.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 20 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.562 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.*1971A>G		3_prime_UTR	Exon 12 of 12	NP_060069.3
	VEZT	NM_001352088.2		c.*1971A>G		3_prime_UTR	Exon 13 of 13	NP_001339017.1
	VEZT	NM_001352089.2		c.*1971A>G		3_prime_UTR	Exon 12 of 12	NP_001339018.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEZT	ENST00000436874.6	TSL:1 MANE Select	c.*1971A>G		3_prime_UTR	Exon 12 of 12	ENSP00000410083.1	Q9HBM0-1
	VEZT	ENST00000851270.1		c.*1971A>G		3_prime_UTR	Exon 12 of 12	ENSP00000521329.1
	VEZT	ENST00000918113.1		c.*1971A>G		3_prime_UTR	Exon 12 of 12	ENSP00000588172.1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73471 AN: 151756 Hom.: 18128 Cov.: 31

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.496

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.484 AC: 73547 AN: 151874 Hom.: 18154 Cov.: 31 AF XY: 0.475 AC XY: 35257 AN XY: 74214

African (AFR) AF: 0.568 AC: 23514 AN: 41406

American (AMR) AF: 0.428 AC: 6532 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1809 AN: 3468

East Asian (EAS) AF: 0.428 AC: 2214 AN: 5168

South Asian (SAS) AF: 0.493 AC: 2364 AN: 4794

European-Finnish (FIN) AF: 0.316 AC: 3326 AN: 10538

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.471 AC: 32009 AN: 67936

Other (OTH) AF: 0.497 AC: 1047 AN: 2108

Alfa AF: 0.489 Hom.: 24969

Bravo AF: 0.496

Asia WGS AF: 0.484 AC: 1678 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.072
DANN	Benign	0.58
PhyloP100		-1.9
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: rs3596; hg19: chr12-95696420;