NM_012384.5:c.*193T>A

Variant names:

• chr20-63589896-A-T
• rs311497
• NM_012384.5:c.*193T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012384.5(GMEB2):​c.*193T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000714 in 280,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: GMEB2 NM_012384.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506
• Publications: 27 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012384.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GMEB2	NM_012384.5	MANE Select	c.*193T>A		3_prime_UTR	Exon 10 of 10	NP_036516.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GMEB2	ENST00000370077.2	TSL:1 MANE Select	c.*193T>A		3_prime_UTR	Exon 10 of 10	ENSP00000359094.1
	GMEB2	ENST00000889844.1		c.*193T>A		3_prime_UTR	Exon 10 of 10	ENSP00000559903.1
	GMEB2	ENST00000889843.1		c.*193T>A		3_prime_UTR	Exon 10 of 10	ENSP00000559902.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000714 AC: 2 AN: 280092 Hom.: 0 Cov.: 4 AF XY: 0.0000139 AC XY: 2 AN XY: 143480

African (AFR) AF: 0.00 AC: 0 AN: 7728

American (AMR) AF: 0.00 AC: 0 AN: 8958

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9768

East Asian (EAS) AF: 0.0000842 AC: 2 AN: 23748

South Asian (SAS) AF: 0.00 AC: 0 AN: 8770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1384

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 178852

Other (OTH) AF: 0.00 AC: 0 AN: 17908

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.64
PhyloP100		-0.51

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

Other links and lift over

dbSNP: rs311497; hg19: chr20-62221249;