chrX-75783599-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_138703.5(MAGEE2):​c.1453G>T​(p.Ala485Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,098,237 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Consequence

MAGEE2
NM_138703.5 missense

Scores

1
2
14

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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29593486).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAGEE2NM_138703.5 linkc.1453G>T p.Ala485Ser 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.1453G>T p.Ala485Ser missense_variant Exon 1 of 1 6 NM_138703.5 ENSP00000362457.2 Q8TD90

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD3 exomes
AF:
0.00000546
AC:
1
AN:
183308
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
67804
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:
0.0000122
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000182
AC:
2
AN:
1098237
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
1
AN XY:
363593
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.00000237
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 24, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1453G>T (p.A485S) alteration is located in exon 1 (coding exon 1) of the MAGEE2 gene. This alteration results from a G to T substitution at nucleotide position 1453, causing the alanine (A) at amino acid position 485 to be replaced by a serine (S). 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
0.24
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.019
T
FATHMM_MKL
Benign
0.31
N
LIST_S2
Benign
0.58
T
M_CAP
Benign
0.0060
T
MetaRNN
Benign
0.30
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
2.0
M
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.093
Sift
Benign
0.032
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.95
P
Vest4
0.41
MutPred
0.61
Gain of disorder (P = 0.0636);
MVP
0.61
MPC
0.082
ClinPred
0.50
T
GERP RS
1.9
Varity_R
0.21
gMVP
0.46

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: rs770142494; hg19: chrX-75003434; API