Variant X-30251271-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_177404.3(MAGEB1):c.778G>A(p.Val260Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,098,230 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.000012 ( 0 hom. 3 hem. )

Consequence

MAGEB1
NM_177404.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.407

Variant links:

Genes affected

MAGEB1 (HGNC:6808): (MAGE family member B1) 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. This gene is localized in the DSS (dosage-sensitive sex reversal) critical region, and expressed in testis and in a significant fraction of tumors of various histological types. This gene and other MAGEB members are clustered on chromosome Xp22-p21. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene, however, the full length nature of some variants has not been defined. [provided by RefSeq, Jul 2008]

MAGEB1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEB1	NM_177404.3 link	c.778G>A	p.Val260Met	missense_variant	2/2	ENST00000397548.4	NP_796379.1	P43366
MAGEB1	NM_002363.5 link	c.778G>A	p.Val260Met	missense_variant	4/4		NP_002354.2	P43366
MAGEB1	NM_177415.3 link	c.778G>A	p.Val260Met	missense_variant	3/3		NP_803134.1	P43366

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAGEB1	ENST00000397548.4 link	c.778G>A	p.Val260Met	missense_variant	2/2	1	NM_177404.3	ENSP00000380681.2	P43366
MAGEB1	ENST00000378981.8 link	c.778G>A	p.Val260Met	missense_variant	4/4	1		ENSP00000368264.3	P43366
MAGEB1	ENST00000397550.6 link	c.778G>A	p.Val260Met	missense_variant	3/3	1		ENSP00000380683.1	P43366

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183507

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

67937

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000722

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000118

AC:

AN:

1098230

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

363584

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000364

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000237

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

May 26, 2024

The c.778G>A (p.V260M) alteration is located in exon 4 (coding exon 1) of the MAGEB1 gene. This alteration results from a G to A substitution at nucleotide position 778, causing the valine (V) at amino acid position 260 to be replaced by a methionine (M). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;T;T

FATHMM_MKL

Benign

0.057

LIST_S2

Uncertain

0.92

.;D;.

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.63

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.6

H;H;H

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.5

N;N;N

REVEL

Benign

0.099

Sift

Uncertain

0.0080

D;D;D

Sift4G

Uncertain

0.017

D;D;D

Polyphen

0.98

D;D;D

Vest4

0.073

MutPred

0.88

Loss of catalytic residue at V260 (P = 0.0473);Loss of catalytic residue at V260 (P = 0.0473);Loss of catalytic residue at V260 (P = 0.0473);

MVP

0.44

MPC

0.28

ClinPred

0.84

GERP RS

1.3

Varity_R

0.13

gMVP

0.39

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