X-142203431-C-A

Variant summary

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

The NM_016249.4(MAGEC2):​c.557G>T​(p.Arg186Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000405 in 1,209,558 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R186C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.000042 ( 0 hom. 16 hem. )

Consequence

MAGEC2
NM_016249.4 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.102
Variant links:
Genes affected
MAGEC2 (HGNC:13574): (MAGE family member C2) This gene is a member of the MAGEC gene family. It is not expressed in normal tissues, except for testis, and is expressed in tumors of various histological types. This gene and the other MAGEC genes are clustered on chromosome Xq26-q27. [provided by RefSeq, Oct 2009]

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=0.09800395).
BS2
High Hemizygotes in GnomAdExome4 at 16 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAGEC2NM_016249.4 linkc.557G>T p.Arg186Leu missense_variant Exon 3 of 3 ENST00000247452.4 NP_057333.1 Q9UBF1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAGEC2ENST00000247452.4 linkc.557G>T p.Arg186Leu missense_variant Exon 3 of 3 1 NM_016249.4 ENSP00000354660.2 Q9UBF1
ENSG00000288098ENST00000664519.1 linkn.300+7647C>A intron_variant Intron 2 of 9

Frequencies

GnomAD3 genomes
AF:
0.0000269
AC:
3
AN:
111662
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33850
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000565
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000382
AC:
7
AN:
183339
Hom.:
0
AF XY:
0.0000590
AC XY:
4
AN XY:
67787
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:
0.000210
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000367
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000419
AC:
46
AN:
1097896
Hom.:
0
Cov.:
33
AF XY:
0.0000440
AC XY:
16
AN XY:
363258
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:
0.000240
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000380
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
AF:
0.0000269
AC:
3
AN:
111662
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33850
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000565
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340
ExAC
AF:
0.0000412
AC:
5

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 21, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.557G>T (p.R186L) alteration is located in exon 3 (coding exon 1) of the MAGEC2 gene. This alteration results from a G to T substitution at nucleotide position 557, causing the arginine (R) at amino acid position 186 to be replaced by a leucine (L). 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
0.20
BayesDel_addAF
Benign
-0.62
T
BayesDel_noAF
Benign
-0.84
CADD
Benign
1.2
DANN
Benign
0.56
DEOGEN2
Benign
0.084
T
FATHMM_MKL
Benign
0.017
N
LIST_S2
Benign
0.062
T
M_CAP
Benign
0.0030
T
MetaRNN
Benign
0.098
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.1
L
PrimateAI
Benign
0.26
T
PROVEAN
Uncertain
-2.7
D
REVEL
Benign
0.019
Sift
Benign
0.14
T
Sift4G
Benign
0.49
T
Polyphen
0.029
B
Vest4
0.051
MutPred
0.70
Gain of ubiquitination at K183 (P = 0.0453);
MVP
0.043
MPC
0.018
ClinPred
0.025
T
GERP RS
-0.088
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.096
gMVP
0.39

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: rs748643907; hg19: chrX-141291217; COSMIC: COSV55999836; API