Variant X-30236880-A-G 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.956A>G(p.Gln319Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000364 in 1,097,890 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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: 0.0000036 ( 0 hom. 3 hem. )

Consequence

MAGEB3
NM_002365.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.605

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=0.047156066).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAGEB3	NM_002365.5 linkuse as main transcript	c.956A>G	p.Gln319Arg	missense_variant	5/5	ENST00000361644.4	NP_002356.2
MAGEB3	NM_001386865.1 linkuse as main transcript	c.956A>G	p.Gln319Arg	missense_variant	3/3		NP_001373794.1
MAGEB3	XM_011545513.3 linkuse as main transcript	c.956A>G	p.Gln319Arg	missense_variant	4/4		XP_011543815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEB3	ENST00000361644.4 linkuse as main transcript	c.956A>G	p.Gln319Arg	missense_variant	5/5	2	NM_002365.5	ENSP00000355198	P1
MAGEB3	ENST00000620842.1 linkuse as main transcript	c.956A>G	p.Gln319Arg	missense_variant	1/1			ENSP00000478513	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000364

AC:

AN:

1097890

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

363248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

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:

0.00000356

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 07, 2024

The c.956A>G (p.Q319R) alteration is located in exon 5 (coding exon 1) of the MAGEB3 gene. This alteration results from a A to G substitution at nucleotide position 956, causing the glutamine (Q) at amino acid position 319 to be replaced by an arginine (R). 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

0.064

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.030

DANN

Benign

0.29

DEOGEN2

Benign

0.019

T;T

FATHMM_MKL

Benign

0.0080

LIST_S2

Benign

0.18

.;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.047

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.54

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.91

N;.

REVEL

Benign

0.0090

Sift

Benign

0.79

T;.

Sift4G

Benign

0.99

T;T

Polyphen

0.0010

B;B

Vest4

0.026

MutPred

0.33

Gain of MoRF binding (P = 0.0362);Gain of MoRF binding (P = 0.0362);

MVP

0.043

MPC

0.13

ClinPred

0.021

GERP RS

-0.44

Varity_R

0.050

gMVP

0.27

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over