X-30218853-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002364.5(MAGEB2):​c.273G>T​(p.Glu91Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Consequence

MAGEB2
NM_002364.5 missense

Scores

2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.417
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07293388).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAGEB2NM_002364.5 linkc.273G>T p.Glu91Asp missense_variant Exon 2 of 2 ENST00000378988.5 NP_002355.2 O15479Q53G50
MAGEB2XM_011545512.2 linkc.273G>T p.Glu91Asp 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.273G>T p.Glu91Asp missense_variant Exon 2 of 2 1 NM_002364.5 ENSP00000368273.4 O15479

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
24

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 05, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.273G>T (p.E91D) alteration is located in exon 2 (coding exon 1) of the MAGEB2 gene. This alteration results from a G to T substitution at nucleotide position 273, causing the glutamic acid (E) at amino acid position 91 to be replaced by an aspartic acid (D). 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
0.13
BayesDel_addAF
Benign
-0.58
T
BayesDel_noAF
Benign
-1.1
CADD
Benign
7.4
DANN
Uncertain
0.99
DEOGEN2
Benign
0.017
T
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.29
T
M_CAP
Benign
0.0019
T
MetaRNN
Benign
0.073
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.21
T
PROVEAN
Uncertain
-2.4
N
REVEL
Benign
0.044
Sift
Benign
0.030
D
Sift4G
Benign
0.063
T
Polyphen
0.26
B
Vest4
0.037
MutPred
0.13
Loss of ubiquitination at K92 (P = 0.1139);
MVP
0.15
MPC
0.0030
ClinPred
0.12
T
GERP RS
1.3
Varity_R
0.21
gMVP
0.097

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-30236970; API