Variant X-30236867-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002365.5(MAGEB3):c.943G>A(p.Glu315Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000901 in 1,210,081 control chromosomes in the GnomAD database, including 1 homozygotes. There are 24 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., 3 hem., cov: 24)

Exomes 𝑓: 0.000076 ( 1 hom. 21 hem. )

Consequence

MAGEB3
NM_002365.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.13

Variant links:

Genes affected

MAGEB3 (HGNC:6810): (MAGE family member B3) This gene is a MAGE-B subfamily member of the MAGE gene family. MAGE family member proteins direct the expression of tumor antigens recognized on a human melanoma by autologous cytolytic T lymphocytes. There are two known clusters of MAGE genes on chromosome X. The members of the MAGE-A subfamily are located in the Xq28 region, while the members of the MAGE-B subfamily are clustered in the Xp21 region. [provided by RefSeq, Jul 2008]

MAGEB3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008831173).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEB3	NM_002365.5 linkuse as main transcript	c.943G>A	p.Glu315Lys	missense_variant	5/5	ENST00000361644.4	NP_002356.2	O15480
MAGEB3	NM_001386865.1 linkuse as main transcript	c.943G>A	p.Glu315Lys	missense_variant	3/3		NP_001373794.1
MAGEB3	XM_011545513.3 linkuse as main transcript	c.943G>A	p.Glu315Lys	missense_variant	4/4		XP_011543815.1	O15480

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEB3	ENST00000361644.4 linkuse as main transcript	c.943G>A	p.Glu315Lys	missense_variant	5/5	2	NM_002365.5	ENSP00000355198.2		O15480
MAGEB3	ENST00000620842.1 linkuse as main transcript	c.943G>A	p.Glu315Lys	missense_variant	1/1	6		ENSP00000478513.1		O15480

Frequencies

GnomAD3 genomes

AF:

0.000232

AC:

AN:

112165

Hom.:

Cov.:

AF XY:

0.0000874

AC XY:

AN XY:

34339

show subpopulations

Gnomad AFR

AF:

0.000227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00112

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000660

GnomAD3 exomes

AF:

0.000158

AC:

AN:

183354

Hom.:

AF XY:

0.0000737

AC XY:

AN XY:

67810

show subpopulations

Gnomad AFR exome

AF:

0.000304

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00152

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.000663

GnomAD4 exome

AF:

0.0000756

AC:

AN:

1097862

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

363216

show subpopulations

Gnomad4 AFR exome

AF:

0.000189

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000861

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.00108

GnomAD4 genome

AF:

0.000232

AC:

AN:

112219

Hom.:

Cov.:

AF XY:

0.0000872

AC XY:

AN XY:

34403

show subpopulations

Gnomad4 AFR

AF:

0.000226

Gnomad4 AMR

AF:

0.00132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00112

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000652

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.000140

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000132

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 30, 2023

The c.943G>A (p.E315K) alteration is located in exon 5 (coding exon 1) of the MAGEB3 gene. This alteration results from a G to A substitution at nucleotide position 943, causing the glutamic acid (E) at amino acid position 315 to be replaced by a lysine (K). 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

0.075

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.79

DANN

Benign

0.89

DEOGEN2

Benign

0.065

T;T

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.74

.;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.0088

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.3

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.2

D;.

REVEL

Benign

0.019

Sift

Benign

0.053

T;.

Sift4G

Benign

0.069

T;T

Polyphen

0.0060

B;B

Vest4

0.14

MVP

0.082

MPC

0.13

ClinPred

0.0062

GERP RS

-3.1

Varity_R

0.16

gMVP

0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over