12-95273561-C-T

Position:

• chr12-95273561-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017599.4(VEZT):​c.849-1181C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,936 control chromosomes in the GnomAD database, including 18,149 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 (18149 hom., cov: 32)
• Consequence: VEZT NM_017599.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VEZT	NM_017599.4	c.849-1181C>T		intron_variant		ENST00000436874.6	NP_060069.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VEZT	ENST00000436874.6	c.849-1181C>T		intron_variant		1	NM_017599.4	ENSP00000410083.1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73495 AN: 151818 Hom.: 18123 Cov.: 32

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.497

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

GnomAD4 genome AF: 0.484 AC: 73568 AN: 151936 Hom.: 18149 Cov.: 32 AF XY: 0.475 AC XY: 35276 AN XY: 74244

Gnomad4 AFR AF: 0.568

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.497

Alfa AF: 0.478 Hom.: 2176

Bravo AF: 0.495

Asia WGS AF: 0.484 AC: 1675 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	13
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs4471514; hg19: chr12-95667337;