Variant chrX-30236942-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002365.5(MAGEB3):c.1018G>A(p.Ala340Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000046 in 1,087,527 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000046 ( 0 hom. 1 hem. )

Consequence

MAGEB3
NM_002365.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.86

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040856928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEB3	NM_002365.5 linkuse as main transcript	c.1018G>A	p.Ala340Thr	missense_variant	5/5	ENST00000361644.4	NP_002356.2	O15480
MAGEB3	NM_001386865.1 linkuse as main transcript	c.1018G>A	p.Ala340Thr	missense_variant	3/3		NP_001373794.1
MAGEB3	XM_011545513.3 linkuse as main transcript	c.1018G>A	p.Ala340Thr	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.1018G>A	p.Ala340Thr	missense_variant	5/5	2	NM_002365.5	ENSP00000355198.2		O15480
MAGEB3	ENST00000620842.1 linkuse as main transcript	c.1018G>A	p.Ala340Thr	missense_variant	1/1	6		ENSP00000478513.1		O15480

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000178

AC:

AN:

168296

Hom.:

AF XY:

0.0000185

AC XY:

AN XY:

54144

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000118

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000460

AC:

AN:

1087527

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

354015

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000887

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000120

Gnomad4 OTH exome

AF:

0.0000219

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

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

Oct 03, 2022

The c.1018G>A (p.A340T) 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 1018, causing the alanine (A) at amino acid position 340 to be replaced by a threonine (T). 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

0.087

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.015

DANN

Benign

0.51

DEOGEN2

Benign

0.018

T;T

FATHMM_MKL

Benign

0.0053

LIST_S2

Benign

0.25

.;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.041

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.47

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.90

N;.

REVEL

Benign

0.011

Sift

Benign

0.66

T;.

Sift4G

Benign

0.19

T;T

Polyphen

0.012

B;B

Vest4

0.035

MutPred

0.18

Gain of phosphorylation at A340 (P = 0.0201);Gain of phosphorylation at A340 (P = 0.0201);

MVP

0.043

MPC

0.12

ClinPred

0.025

GERP RS

-8.4

Varity_R

0.037

gMVP

0.19

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