Variant chr10-133239972-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000325980.10(VENTX):c.443G>A(p.Arg148Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000292 in 1,611,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

VENTX
ENST00000325980.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.60

Variant links:

Genes affected

VENTX (HGNC:13639): (VENT homeobox) This gene encodes a member of the Vent family of homeodomain proteins. The encoded protein may function as a transcriptional repressor and be involved in mesodermal patterning and hemopoietic stem cell maintenance. Multiple pseudogenes exist for this gene. A transcribed pseudogene located on chromosome X may lead to antigen production in certain melanomas. [provided by RefSeq, Jul 2008]

VENTX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41329587).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VENTX	NM_014468.4 linkuse as main transcript	c.443G>A	p.Arg148Gln	missense_variant	3/3	ENST00000325980.10	NP_055283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VENTX	ENST00000325980.10 linkuse as main transcript	c.443G>A	p.Arg148Gln	missense_variant	3/3	1	NM_014468.4	ENSP00000357556	P1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000240

AC:

AN:

249710

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135194

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1459428

Hom.:

Cov.:

AF XY:

0.0000207

AC XY:

AN XY:

726154

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.000105

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.000386

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.443G>A (p.R148Q) alteration is located in exon 3 (coding exon 3) of the VENTX gene. This alteration results from a G to A substitution at nucleotide position 443, causing the arginine (R) at amino acid position 148 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.054

BayesDel_noAF

Uncertain

0.040

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.60

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.30

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.074

MetaRNN

Benign

0.41

MetaSVM

Pathogenic

0.87

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

0.96

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.50

Sift

Uncertain

0.0020

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.28

MVP

0.62

MPC

0.37

ClinPred

0.56

GERP RS

0.91

Varity_R

0.45

gMVP

0.27

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over