20-63592117-T-C

Position:

• chr20-63592117-T-C

Variant summary

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

The NM_012384.5(GMEB2):​c.857A>G​(p.Gln286Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GMEB2 NM_012384.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.53

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.857A>G	p.Gln286Arg	missense_variant	9/10	ENST00000370077.2	NP_036516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GMEB2	ENST00000370077.2	c.857A>G	p.Gln286Arg	missense_variant	9/10	1	NM_012384.5	ENSP00000359094.1
GMEB2	ENST00000266068.5	c.857A>G	p.Gln286Arg	missense_variant	8/9	2		ENSP00000266068.1
GMEB2	ENST00000370069.5	c.704A>G	p.Gln235Arg	missense_variant	7/8	5		ENSP00000359086.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Feb 22, 2023

The c.857A>G (p.Q286R) alteration is located in exon 9 (coding exon 8) of the GMEB2 gene. This alteration results from a A to G substitution at nucleotide position 857, causing the glutamine (Q) at amino acid position 286 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	0.25
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.087	.;T;T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D;.;D
M_CAP	Benign	0.065	D
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Uncertain	2.2	.;M;M
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.031	D;D;D
Sift4G	Benign	0.10	T;T;T
Polyphen		0.98	.;D;D
Vest4		0.80
MutPred		0.52		.;Gain of MoRF binding (P = 0.0176);Gain of MoRF binding (P = 0.0176);
MVP		0.52
MPC		0.82
ClinPred		0.80	D
GERP RS		5.3
Varity_R		0.35
gMVP		0.66

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: chr20-62223470;