Variant 20-63590457-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_012384.5(GMEB2):c.1225G>A(p.Val409Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,520,934 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 1 hom. )

Consequence

GMEB2
NM_012384.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.768

Variant links:

Genes affected

GMEB2 (HGNC:4371): (glucocorticoid modulatory element binding protein 2) This gene is a member of KDWK gene family. The product of this gene associates with GMEB1 protein, and the complex is essential for parvovirus DNA replication. Study of rat homolog implicates the role of this gene in modulation of transactivation by the glucocorticoid receptor bound to glucocorticoid response elements. This gene appears to use multiple polyadenylation sites. [provided by RefSeq, Jul 2008]

GMEB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021492273).

BS2

High AC in GnomAd4 at 77 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GMEB2	NM_012384.5 linkuse as main transcript	c.1225G>A	p.Val409Ile	missense_variant	10/10	ENST00000370077.2	NP_036516.1	Q9UKD1B4DQS0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GMEB2	ENST00000370077.2 linkuse as main transcript	c.1225G>A	p.Val409Ile	missense_variant	10/10	1	NM_012384.5	ENSP00000359094.1	Q9UKD1
GMEB2	ENST00000266068.5 linkuse as main transcript	c.1225G>A	p.Val409Ile	missense_variant	9/9	2		ENSP00000266068.1	Q9UKD1
GMEB2	ENST00000370069.5 linkuse as main transcript	c.1072G>A	p.Val358Ile	missense_variant	8/8	5		ENSP00000359086.1	Q5JTV1

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000882

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000519

AC:

AN:

148400

Hom.:

AF XY:

0.000420

AC XY:

AN XY:

78584

show subpopulations

Gnomad AFR exome

AF:

0.000386

Gnomad AMR exome

AF:

0.0000960

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000155

Gnomad SAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00103

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00128

AC:

1747

AN:

1368614

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

804

AN XY:

669522

show subpopulations

Gnomad4 AFR exome

AF:

0.000126

Gnomad4 AMR exome

AF:

0.0000618

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000270

Gnomad4 SAS exome

AF:

0.000173

Gnomad4 FIN exome

AF:

0.0000414

Gnomad4 NFE exome

AF:

0.00158

Gnomad4 OTH exome

AF:

0.000939

GnomAD4 genome

AF:

0.000506

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000882

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000948

Hom.:

Bravo

AF:

0.000574

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000464

AC:

ESP6500EA

AF:

0.00141

AC:

ExAC

AF:

0.000329

AC:

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 20, 2024

The c.1225G>A (p.V409I) alteration is located in exon 10 (coding exon 9) of the GMEB2 gene. This alteration results from a G to A substitution at nucleotide position 1225, causing the valine (V) at amino acid position 409 to be replaced by an isoleucine (I). 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

0.079

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.89

DANN

Benign

0.83

DEOGEN2

Benign

0.029

.;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.098

LIST_S2

Benign

0.49

T;.;T

M_CAP

Benign

0.043

MetaRNN

Benign

0.021

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

.;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.28

N;N;N

REVEL

Benign

0.019

Sift

Benign

0.27

T;T;T

Sift4G

Benign

0.58

T;T;T

Polyphen

0.0030

.;B;B

Vest4

0.031

MVP

0.35

MPC

0.47

ClinPred

0.0018

GERP RS

-3.4

Varity_R

0.031

gMVP

0.15

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