X-75783769-C-T

Variant summary

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

The NM_138703.5(MAGEE2):​c.1283G>A​(p.Arg428Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000228 in 1,098,222 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 0.000023 ( 0 hom. 4 hem. )

Consequence

MAGEE2
NM_138703.5 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.276
Variant links:
Genes affected
MAGEE2 (HGNC:24935): (MAGE family member E2) This gene encodes a member of the E subfamily of MAGE (melanoma antigen-encoding gene) gene family. The gene is intronless and the encoded protein has two of the MAGE domains which are characteristic of MAGE family proteins. [provided by RefSeq, Sep 2011]

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=0.08185521).
BS2
High Hemizygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAGEE2NM_138703.5 linkc.1283G>A p.Arg428Gln missense_variant Exon 1 of 1 ENST00000373359.4 NP_619648.1 Q8TD90

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAGEE2ENST00000373359.4 linkc.1283G>A p.Arg428Gln missense_variant Exon 1 of 1 6 NM_138703.5 ENSP00000362457.2 Q8TD90

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD3 exomes
AF:
0.0000109
AC:
2
AN:
183254
Hom.:
0
AF XY:
0.0000148
AC XY:
1
AN XY:
67772
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000245
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000228
AC:
25
AN:
1098222
Hom.:
0
Cov.:
31
AF XY:
0.0000110
AC XY:
4
AN XY:
363576
show subpopulations
Gnomad4 AFR exome
AF:
0.0000379
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000185
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000226
Gnomad4 OTH exome
AF:
0.0000651
GnomAD4 genome
Cov.:
23
ExAC
AF:
0.0000247
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 12, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1283G>A (p.R428Q) alteration is located in exon 1 (coding exon 1) of the MAGEE2 gene. This alteration results from a G to A substitution at nucleotide position 1283, causing the arginine (R) at amino acid position 428 to be replaced by a glutamine (Q). 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
0.094
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-1.0
CADD
Benign
1.6
DANN
Benign
0.87
DEOGEN2
Benign
0.020
T
FATHMM_MKL
Benign
0.0096
N
LIST_S2
Benign
0.52
T
M_CAP
Benign
0.0020
T
MetaRNN
Benign
0.082
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.9
M
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.050
Sift
Benign
0.062
T
Sift4G
Benign
0.23
T
Polyphen
0.0070
B
Vest4
0.075
MutPred
0.53
Loss of phosphorylation at S431 (P = 0.0543);
MVP
0.24
MPC
0.012
ClinPred
0.043
T
GERP RS
-2.9
Varity_R
0.068
gMVP
0.31

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: rs772582645; hg19: chrX-75003604; COSMIC: COSV64898367; API