Variant 10-133240193-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000325980.10(VENTX):c.664G>A(p.Gly222Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,609,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

VENTX
ENST00000325980.10 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.22

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024194509).

BP6

Variant 10-133240193-G-A is Benign according to our data. Variant chr10-133240193-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2204872.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VENTX	NM_014468.4 linkuse as main transcript	c.664G>A	p.Gly222Arg	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.664G>A	p.Gly222Arg	missense_variant	3/3	1	NM_014468.4	ENSP00000357556	P1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000333

AC:

AN:

240158

Hom.:

AF XY:

0.0000303

AC XY:

AN XY:

131800

show subpopulations

Gnomad AFR exome

AF:

0.000141

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000462

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1457674

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

725214

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.000121

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000331

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.0030

DANN

Benign

0.19

DEOGEN2

Benign

0.0037

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.0010

LIST_S2

Benign

0.31

M_CAP

Benign

0.060

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.67

MutationAssessor

Benign

-0.46

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

0.040

REVEL

Benign

0.19

Sift

Benign

0.95

Sift4G

Benign

0.32

Polyphen

0.0

Vest4

0.068

MutPred

0.28

Gain of methylation at G222 (P = 0.0382);

MVP

0.21

MPC

0.10

ClinPred

0.0098

GERP RS

-4.6

Varity_R

0.047

gMVP

0.087

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