chrX-75783863-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.1189G>A​(p.Gly397Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,210,130 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 49 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., 4 hem., cov: 22)
Exomes 𝑓: 0.00013 ( 0 hom. 45 hem. )

Consequence

MAGEE2
NM_138703.5 missense

Scores

6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.33
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=0.17636997).
BS2
High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAGEE2NM_138703.5 linkc.1189G>A p.Gly397Arg 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.1189G>A p.Gly397Arg missense_variant Exon 1 of 1 6 NM_138703.5 ENSP00000362457.2 Q8TD90

Frequencies

GnomAD3 genomes
AF:
0.000143
AC:
16
AN:
111872
Hom.:
0
Cov.:
22
AF XY:
0.000117
AC XY:
4
AN XY:
34054
show subpopulations
Gnomad AFR
AF:
0.0000325
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.000282
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000328
AC:
6
AN:
183188
Hom.:
0
AF XY:
0.0000443
AC XY:
3
AN XY:
67718
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:
0.0000734
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000130
AC:
143
AN:
1098204
Hom.:
0
Cov.:
31
AF XY:
0.000124
AC XY:
45
AN XY:
363574
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000164
Gnomad4 OTH exome
AF:
0.0000868
GnomAD4 genome
AF:
0.000143
AC:
16
AN:
111926
Hom.:
0
Cov.:
22
AF XY:
0.000117
AC XY:
4
AN XY:
34118
show subpopulations
Gnomad4 AFR
AF:
0.0000324
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000282
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000139
Hom.:
4
Bravo
AF:
0.0000831
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000149
AC:
1
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.000237

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 15, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1189G>A (p.G397R) 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 1189, causing the glycine (G) at amino acid position 397 to be replaced by an arginine (R). 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
Uncertain
0.39
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.016
T
FATHMM_MKL
Benign
0.29
N
LIST_S2
Benign
0.66
T
M_CAP
Benign
0.0061
T
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-1.4
N
REVEL
Benign
0.14
Sift
Uncertain
0.0080
D
Sift4G
Uncertain
0.0040
D
Polyphen
1.0
D
Vest4
0.30
MutPred
0.49
Gain of solvent accessibility (P = 0.0037);
MVP
0.21
MPC
0.084
ClinPred
0.33
T
GERP RS
1.9
Varity_R
0.12
gMVP
0.42

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: rs41310679; hg19: chrX-75003698; API