Genetic Variant NM_002365.5:c.652G>A (chrX-30236576-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_002365.5(MAGEB3):c.652G>A(p.Ala218Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000729 in 1,097,743 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A218V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000073 ( 0 hom. 6 hem. )

Consequence

MAGEB3
NM_002365.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.97

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002365.5. 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
	MAGEB3	NM_002365.5	MANE Select	c.652G>A	p.Ala218Thr	missense	Exon 5 of 5	NP_002356.2
	MAGEB3	NM_001386865.1		c.652G>A	p.Ala218Thr	missense	Exon 3 of 3	NP_001373794.1	O15480

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEB3	ENST00000361644.4	TSL:2 MANE Select	c.652G>A	p.Ala218Thr	missense	Exon 5 of 5	ENSP00000355198.2	O15480
	MAGEB3	ENST00000620842.1	TSL:6	c.652G>A	p.Ala218Thr	missense	Exon 1 of 1	ENSP00000478513.1	O15480

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000660

AC:

AN:

181752

AF XY:

0.0000603

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000873

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000729

AC:

AN:

1097743

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

363101

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26398

American (AMR)

AF:

0.00

AC:

AN:

35167

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19376

East Asian (EAS)

AF:

0.000265

AC:

AN:

30197

South Asian (SAS)

AF:

0.00

AC:

AN:

54064

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40515

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841809

Other (OTH)

AF:

0.00

AC:

AN:

46081

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000412

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.081

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.83

M_CAP

Benign

0.051

MetaRNN

Uncertain

0.56

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

PhyloP100

4.0

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.20

Sift

Uncertain

0.016

Sift4G

Uncertain

0.030

Polyphen

1.0

Vest4

0.40

MutPred

0.83

Gain of ubiquitination at K222 (P = 0.1111)

MVP

0.40

MPC

0.54

ClinPred

0.52

GERP RS

4.3

Varity_R

0.23

gMVP

0.58

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over