8-109564525-A-G

Position:

• chr8-109564525-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004215.5(EBAG9):​c.608A>G​(p.Lys203Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: EBAG9 NM_004215.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.30

Genes affected

EBAG9 (HGNC:3123): (estrogen receptor binding site associated antigen 9) This gene was identified as an estrogen-responsive gene. Regulation of transcription by estrogen is mediated by estrogen receptor, which binds to the estrogen-responsive element found in the 5'-flanking region of this gene. The encoded protein is a tumor-associated antigen that is expressed at high frequency in a variety of cancers. Alternate splicing results in multiple transcript variants. A pseudogene of this gene has been defined on chromosome 10. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2911688).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EBAG9	NM_004215.5	c.608A>G	p.Lys203Arg	missense_variant	7/7	ENST00000337573.10	NP_004206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EBAG9	ENST00000337573.10	c.608A>G	p.Lys203Arg	missense_variant	7/7	1	NM_004215.5	ENSP00000337675	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Mar 07, 2023

The c.608A>G (p.K203R) alteration is located in exon 7 (coding exon 6) of the EBAG9 gene. This alteration results from a A to G substitution at nucleotide position 608, causing the lysine (K) at amino acid position 203 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	0.13
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;.;T;T;.
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	.;D;.;D;.
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.29	T;T;T;T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.0	L;.;L;L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.84	N;.;N;.;N
REVEL	Uncertain	0.29
Sift	Benign	0.077	T;.;T;.;D
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		1.0	D;.;D;D;.
Vest4		0.46
MutPred		0.12		Loss of methylation at K203 (P = 0.0355);.;Loss of methylation at K203 (P = 0.0355);Loss of methylation at K203 (P = 0.0355);.;
MVP		0.28
MPC		0.90
ClinPred		0.87	D
GERP RS		5.6
Varity_R		0.10
gMVP		0.16

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: chr8-110576754; COSMIC: COSV61752792; COSMIC: COSV61752792;