chr12-95282570-G-C

Position:

• chr12-95282570-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017599.4(VEZT):​c.1254G>C​(p.Gln418His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: VEZT NM_017599.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.57

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25137752).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VEZT	NM_017599.4	c.1254G>C	p.Gln418His	missense_variant	8/12	ENST00000436874.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VEZT	ENST00000436874.6	c.1254G>C	p.Gln418His	missense_variant	8/12	1	NM_017599.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000241 AC: 6 AN: 248994 Hom.: 0 AF XY: 0.0000222 AC XY: 3 AN XY: 135058

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000334

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461670 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727118

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T;T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	L;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.8	N;N;.
REVEL	Benign	0.085
Sift	Benign	0.18	T;T;.
Sift4G	Uncertain	0.016	D;D;D
Polyphen		0.90	P;.;.
Vest4		0.36
MutPred		0.32		Gain of catalytic residue at L413 (P = 0.0012);.;.;
MVP		0.55
MPC		0.32
ClinPred		0.71	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.043
gMVP		0.31

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: rs1388130301; hg19: chr12-95676346;