8-109553933-T-C

Variant names:

• chr8-109553933-T-C
• NM_004215.5:c.152T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004215.5(EBAG9):​c.152T>C​(p.Val51Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 4.44
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19826871).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004215.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBAG9	NM_004215.5	MANE Select	c.152T>C	p.Val51Ala	missense	Exon 3 of 7	NP_004206.1	O00559-1
	EBAG9	NM_001278938.2		c.152T>C	p.Val51Ala	missense	Exon 3 of 7	NP_001265867.1	O00559-1
	EBAG9	NM_198120.3		c.152T>C	p.Val51Ala	missense	Exon 3 of 7	NP_936056.1	O00559-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBAG9	ENST00000337573.10	TSL:1 MANE Select	c.152T>C	p.Val51Ala	missense	Exon 3 of 7	ENSP00000337675.5	O00559-1
	EBAG9	ENST00000531677.5	TSL:1	c.152T>C	p.Val51Ala	missense	Exon 2 of 7	ENSP00000432082.1	O00559-2
	EBAG9	ENST00000395785.7	TSL:1	c.152T>C	p.Val51Ala	missense	Exon 3 of 7	ENSP00000379131.2	O00559-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.046
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.4
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.029
Sift	Benign	0.055	T
Sift4G	Benign	0.10	T
Polyphen		0.010	B
Vest4		0.34
MutPred		0.17		Loss of stability (P = 0.0625)
MVP		0.13
MPC		0.39
ClinPred		0.70	D
GERP RS		4.4
Varity_R		0.058
gMVP		0.65
Mutation Taster		=70/30	polymorphism

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

hg19: chr8-110566162;