Variant X-30242968-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002367.4(MAGEB4):c.833C>A(p.Ala278Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,098,122 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000027 ( 0 hom. 0 hem. )

Consequence

MAGEB4
NM_002367.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.216

Variant links:

Genes affected

MAGEB4 (HGNC:6811): (MAGE family member B4) This gene is a member of the MAGEB gene family. The members of this family have their entire coding sequences located in the last exon, and the encoded proteins show 50 to 68% sequence identity to each other. The promoters and first exons of the MAGEB genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. The MAGEB genes are clustered on chromosome Xp22-p21. This gene sequence ends in the first intron of MAGEB1, another family member. This gene is expressed in testis. [provided by RefSeq, Jul 2008]

MAGEB4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36631423).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEB4	NM_002367.4 linkuse as main transcript	c.833C>A	p.Ala278Glu	missense_variant	1/1	ENST00000378982.4	NP_002358.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEB4	ENST00000378982.4 linkuse as main transcript	c.833C>A	p.Ala278Glu	missense_variant	1/1		NM_002367.4	ENSP00000368266	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000273

AC:

AN:

1098122

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363476

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

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

Jan 04, 2024

The c.833C>A (p.A278E) alteration is located in exon 1 (coding exon 1) of the MAGEB4 gene. This alteration results from a C to A substitution at nucleotide position 833, causing the alanine (A) at amino acid position 278 to be replaced by a glutamic acid (E). 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

0.23

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.16

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.71

M_CAP

Benign

0.0078

MetaRNN

Benign

0.37

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.060

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.18

MutPred

0.70

Gain of ubiquitination at K282 (P = 0.0353);

MVP

0.21

MPC

0.58

ClinPred

1.0

GERP RS

0.34

Varity_R

0.72

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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