chrX-30250976-T-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PP3_StrongBS2

The NM_177404.3(MAGEB1):c.483T>G(p.Phe161Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000578 in 1,210,269 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000055 ( 0 hom. 2 hem. )

Consequence

MAGEB1
NM_177404.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.11

Publications

3 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: Uncertain_significance. The variant received 0 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.965

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEB1	NM_177404.3 link	c.483T>G	p.Phe161Leu	missense_variant	Exon 2 of 2	ENST00000397548.4	NP_796379.1	P43366
MAGEB1	NM_002363.5 link	c.483T>G	p.Phe161Leu	missense_variant	Exon 4 of 4		NP_002354.2	P43366
MAGEB1	NM_177415.3 link	c.483T>G	p.Phe161Leu	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.483T>G	p.Phe161Leu	missense_variant	Exon 2 of 2	1	NM_177404.3	ENSP00000380681.2	P43366
MAGEB1	ENST00000378981.8 link	c.483T>G	p.Phe161Leu	missense_variant	Exon 4 of 4	1		ENSP00000368264.3	P43366
MAGEB1	ENST00000397550.6 link	c.483T>G	p.Phe161Leu	missense_variant	Exon 3 of 3	1		ENSP00000380683.1	P43366

Frequencies

GnomAD3 genomes

AF:

0.00000890

AC:

AN:

112346

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000936

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000548

AC:

AN:

182437

AF XY:

0.0000149

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000546

AC:

AN:

1097923

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

363285

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26400

American (AMR)

AF:

0.0000568

AC:

AN:

35193

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19376

East Asian (EAS)

AF:

0.00

AC:

AN:

30205

South Asian (SAS)

AF:

0.00

AC:

AN:

54034

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40527

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00000475

AC:

AN:

841960

Other (OTH)

AF:

0.00

AC:

AN:

46091

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000890

AC:

AN:

112346

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34510

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30918

American (AMR)

AF:

0.0000936

AC:

AN:

10683

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3567

South Asian (SAS)

AF:

0.00

AC:

AN:

2653

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6192

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53236

Other (OTH)

AF:

0.00

AC:

AN:

1518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

May 17, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.483T>G (p.F161L) alteration is located in exon 4 (coding exon 1) of the MAGEB1 gene. This alteration results from a T to G substitution at nucleotide position 483, causing the phenylalanine (F) at amino acid position 161 to be replaced by a leucine (L). 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

Pathogenic

0.99

BayesDel_addAF

Uncertain

0.043

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T;T

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.75

.;T;.

M_CAP

Benign

0.010

MetaRNN

Pathogenic

0.97

D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.6

H;H;H

PhyloP100

1.1

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-6.0

D;D;D

REVEL

Uncertain

0.32

Sift

Benign

0.034

D;D;D

Sift4G

Uncertain

0.013

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.68

MutPred

0.97

Gain of ubiquitination at K166 (P = 0.0624);Gain of ubiquitination at K166 (P = 0.0624);Gain of ubiquitination at K166 (P = 0.0624);

MVP

0.81

MPC

0.35

ClinPred

0.93

GERP RS

1.6

Varity_R

0.85

gMVP

0.76

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.

chrX-30250976-T-G

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