20-63590219-T-C

Position:

• chr20-63590219-T-C

Variant summary

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

The NM_012384.5(GMEB2):​c.1463A>G​(p.Gln488Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GMEB2 NM_012384.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.50

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GMEB2	NM_012384.5	c.1463A>G	p.Gln488Arg	missense_variant	10/10	ENST00000370077.2	NP_036516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GMEB2	ENST00000370077.2	c.1463A>G	p.Gln488Arg	missense_variant	10/10	1	NM_012384.5	ENSP00000359094.1
GMEB2	ENST00000266068.5	c.1463A>G	p.Gln488Arg	missense_variant	9/9	2		ENSP00000266068.1
GMEB2	ENST00000370069.5	c.1310A>G	p.Gln437Arg	missense_variant	8/8	5		ENSP00000359086.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1458198 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725408

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 06, 2023

The c.1463A>G (p.Q488R) alteration is located in exon 10 (coding exon 9) of the GMEB2 gene. This alteration results from a A to G substitution at nucleotide position 1463, causing the glutamine (Q) at amino acid position 488 to be replaced by an arginine (R). 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	0.17
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	.;T;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.77	T;.;T
M_CAP	Benign	0.076	D
MetaRNN	Uncertain	0.58	D;D;D
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.0	.;M;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.0	N;N;N
REVEL	Benign	0.25
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		0.96	.;P;P
Vest4		0.72
MutPred		0.37		.;Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);
MVP		0.83
MPC		1.6
ClinPred		0.88	D
GERP RS		5.4
Varity_R		0.32
gMVP		0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-62221572;