chrX-30251040-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_177404.3(MAGEB1):​c.547C>G​(p.Leu183Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,516 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. 14/21 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: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

MAGEB1
NM_177404.3 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.39

Publications

0 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28133965).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAGEB1NM_177404.3 linkc.547C>G p.Leu183Val missense_variant Exon 2 of 2 ENST00000397548.4 NP_796379.1 P43366
MAGEB1NM_002363.5 linkc.547C>G p.Leu183Val missense_variant Exon 4 of 4 NP_002354.2 P43366
MAGEB1NM_177415.3 linkc.547C>G p.Leu183Val missense_variant Exon 3 of 3 NP_803134.1 P43366

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAGEB1ENST00000397548.4 linkc.547C>G p.Leu183Val missense_variant Exon 2 of 2 1 NM_177404.3 ENSP00000380681.2 P43366
MAGEB1ENST00000378981.8 linkc.547C>G p.Leu183Val missense_variant Exon 4 of 4 1 ENSP00000368264.3 P43366
MAGEB1ENST00000397550.6 linkc.547C>G p.Leu183Val missense_variant Exon 3 of 3 1 ENSP00000380683.1 P43366

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD2 exomes
AF:
0.00000552
AC:
1
AN:
181123
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000124
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
9.11e-7
AC:
1
AN:
1097516
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
362890
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
26395
American (AMR)
AF:
0.00
AC:
0
AN:
35160
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19375
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30198
South Asian (SAS)
AF:
0.00
AC:
0
AN:
53900
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
40508
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4137
European-Non Finnish (NFE)
AF:
0.00000119
AC:
1
AN:
841766
Other (OTH)
AF:
0.00
AC:
0
AN:
46077
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
23
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 03, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.547C>G (p.L183V) alteration is located in exon 4 (coding exon 1) of the MAGEB1 gene. This alteration results from a C to G substitution at nucleotide position 547, causing the leucine (L) at amino acid position 183 to be replaced by a valine (V). 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
0.12
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.039
DANN
Benign
0.91
DEOGEN2
Benign
0.11
T;T;T
FATHMM_MKL
Benign
0.018
N
LIST_S2
Benign
0.032
.;T;.
M_CAP
Benign
0.0033
T
MetaRNN
Benign
0.28
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
M;M;M
PhyloP100
-2.4
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-1.1
N;N;N
REVEL
Benign
0.084
Sift
Benign
0.12
T;T;T
Sift4G
Benign
0.061
T;T;T
Polyphen
0.080
B;B;B
Vest4
0.029
MutPred
0.79
Loss of stability (P = 0.089);Loss of stability (P = 0.089);Loss of stability (P = 0.089);
MVP
0.32
MPC
0.053
ClinPred
0.069
T
GERP RS
-6.9
Varity_R
0.075
gMVP
0.14
Mutation Taster
=98/2
polymorphism

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

Other links and lift over

dbSNP: rs759970013; hg19: chrX-30269157; API