X-30250960-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_177404.3(MAGEB1):c.467G>A(p.Arg156His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000256 in 1,209,814 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R156L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., 2 hem., cov: 24)

Exomes 𝑓: 0.000022 ( 0 hom. 10 hem. )

Consequence

MAGEB1
NM_177404.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.185

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04433748).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEB1	NM_177404.3 link	c.467G>A	p.Arg156His	missense_variant	Exon 2 of 2	ENST00000397548.4	NP_796379.1	P43366
MAGEB1	NM_002363.5 link	c.467G>A	p.Arg156His	missense_variant	Exon 4 of 4		NP_002354.2	P43366
MAGEB1	NM_177415.3 link	c.467G>A	p.Arg156His	missense_variant	Exon 3 of 3		NP_803134.1	P43366

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAGEB1	ENST00000397548.4 link	c.467G>A	p.Arg156His	missense_variant	Exon 2 of 2	1	NM_177404.3	ENSP00000380681.2	P43366
MAGEB1	ENST00000378981.8 link	c.467G>A	p.Arg156His	missense_variant	Exon 4 of 4	1		ENSP00000368264.3	P43366
MAGEB1	ENST00000397550.6 link	c.467G>A	p.Arg156His	missense_variant	Exon 3 of 3	1		ENSP00000380683.1	P43366

Frequencies

GnomAD3 genomes

AF:

0.0000624

AC:

AN:

112218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000280

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000113

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000219

AC:

AN:

182558

AF XY:

0.0000149

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000368

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1097596

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

362964

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26394

American (AMR)

AF:

0.0000284

AC:

AN:

35186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19371

East Asian (EAS)

AF:

0.00

AC:

AN:

30194

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54020

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40510

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.0000249

AC:

AN:

841702

Other (OTH)

AF:

0.0000217

AC:

AN:

46082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000624

AC:

AN:

112218

Hom.:

Cov.:

AF XY:

0.0000582

AC XY:

AN XY:

34392

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30893

American (AMR)

AF:

0.00

AC:

AN:

10662

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.000280

AC:

AN:

3572

South Asian (SAS)

AF:

0.00

AC:

AN:

2646

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.000113

AC:

AN:

53216

Other (OTH)

AF:

0.00

AC:

AN:

1516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 16, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.467G>A (p.R156H) 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 467, causing the arginine (R) at amino acid position 156 to be replaced by a histidine (H). 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

0.15

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.98

CADD

Benign

2.6

(source)

DANN

Benign

0.13

DEOGEN2

Benign

0.0058

T;T;T

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.12

.;T;.

M_CAP

Benign

0.0039

MetaRNN

Benign

0.044

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.27

N;N;N

PhyloP100

-0.18

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.99

N;N;N

REVEL

Benign

0.037

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.78

T;T;T

Polyphen

0.24

B;B;B

Vest4

0.038

MVP

0.61

MPC

0.092

ClinPred

0.040

GERP RS

-1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.17

Mutation Taster

=100/0

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.

X-30250960-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over