Genetic Variant MAGEB3:p.Ser101Tyr (chrX-30236226-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002365.5(MAGEB3):c.302C>A(p.Ser101Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,096,705 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000027 ( 0 hom. 2 hem. )

Consequence

MAGEB3
NM_002365.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.09

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.086264074).

BS2

High Hemizygotes in GnomAdExome4 at 2 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.302C>A	p.Ser101Tyr	missense	Exon 5 of 5	NP_002356.2
	MAGEB3	NM_001386865.1		c.302C>A	p.Ser101Tyr	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.302C>A	p.Ser101Tyr	missense	Exon 5 of 5	ENSP00000355198.2	O15480
	MAGEB3	ENST00000620842.1	TSL:6	c.302C>A	p.Ser101Tyr	missense	Exon 1 of 1	ENSP00000478513.1	O15480

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000110

AC:

AN:

181628

AF XY:

0.0000151

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000247

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1096705

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

362099

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26361

American (AMR)

AF:

0.00

AC:

AN:

35145

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19362

East Asian (EAS)

AF:

0.00

AC:

AN:

30194

South Asian (SAS)

AF:

0.00

AC:

AN:

53945

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40460

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4127

European-Non Finnish (NFE)

AF:

0.00000357

AC:

AN:

841061

Other (OTH)

AF:

0.00

AC:

AN:

46050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00000824

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

0.094

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.34

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.018

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.18

M_CAP

Benign

0.033

MetaRNN

Benign

0.086

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.3

PhyloP100

-1.1

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.4

REVEL

Benign

0.0050

Sift

Benign

0.18

Sift4G

Benign

0.12

Polyphen

0.010

Vest4

0.14

MVP

0.043

MPC

0.15

ClinPred

0.020

GERP RS

-0.59

PromoterAI

-0.0069

Neutral

(source)

Varity_R

0.064

gMVP

0.077

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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