X-30219012-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002364.5(MAGEB2):​c.432G>T​(p.Arg144Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 1,209,183 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.0000046 ( 0 hom. 2 hem. )

Consequence

MAGEB2
NM_002364.5 missense

Scores

2
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0850
Variant links:
Genes affected
MAGEB2 (HGNC:6809): (MAGE family member B2) 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. It is expressed in testis and placenta, and in a significant fraction of tumors of various histological types. The MAGEB genes are clustered on chromosome Xp22-p21. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.095965415).
BS2
High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAGEB2NM_002364.5 linkc.432G>T p.Arg144Ser missense_variant Exon 2 of 2 ENST00000378988.5 NP_002355.2 O15479Q53G50
MAGEB2XM_011545512.2 linkc.432G>T p.Arg144Ser missense_variant Exon 2 of 2 XP_011543814.1 O15479

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAGEB2ENST00000378988.5 linkc.432G>T p.Arg144Ser missense_variant Exon 2 of 2 1 NM_002364.5 ENSP00000368273.4 O15479

Frequencies

GnomAD3 genomes
AF:
0.0000268
AC:
3
AN:
111981
Hom.:
0
Cov.:
23
AF XY:
0.0000293
AC XY:
1
AN XY:
34151
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000283
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
GnomAD3 exomes
AF:
0.0000166
AC:
3
AN:
180363
Hom.:
0
AF XY:
0.0000154
AC XY:
1
AN XY:
64943
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000736
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000545
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000456
AC:
5
AN:
1097202
Hom.:
0
Cov.:
32
AF XY:
0.00000552
AC XY:
2
AN XY:
362580
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000569
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000186
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000119
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
AF:
0.0000268
AC:
3
AN:
111981
Hom.:
0
Cov.:
23
AF XY:
0.0000293
AC XY:
1
AN XY:
34151
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000283
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000491

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.34
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.84
CADD
Benign
12
DANN
Benign
0.93
DEOGEN2
Benign
0.019
T
FATHMM_MKL
Benign
0.048
N
LIST_S2
Benign
0.066
T
M_CAP
Benign
0.0037
T
MetaRNN
Benign
0.096
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Uncertain
2.1
M
PrimateAI
Benign
0.33
T
PROVEAN
Uncertain
-4.3
D
REVEL
Benign
0.010
Sift
Benign
0.14
T
Sift4G
Benign
0.14
T
Polyphen
0.24
B
Vest4
0.14
MutPred
0.46
Loss of MoRF binding (P = 0.03);
MVP
0.62
MPC
0.0030
ClinPred
0.10
T
GERP RS
-0.88
Varity_R
0.31
gMVP
0.23

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.

Other links and lift over

dbSNP: rs368299444; hg19: chrX-30237129; COSMIC: COSV66780239; API