X-141879413-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_138702.1(MAGEC3):ā€‹c.497G>Cā€‹(p.Trp166Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000127 in 1,179,593 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000082 ( 0 hom., 4 hem., cov: 21)
Exomes š‘“: 0.0000056 ( 0 hom. 2 hem. )

Consequence

MAGEC3
NM_138702.1 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45
Variant links:
Genes affected
MAGEC3 (HGNC:23798): (MAGE family member C3) This gene is a member of the MAGEC gene family. The members of this family are not expressed in normal tissues, except for testis, and are expressed in tumors of various histological types. The MAGEC genes are clustered on chromosome Xq26-q27. Two transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.040317297).
BS2
High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MAGEC3NM_138702.1 linkuse as main transcriptc.497G>C p.Trp166Ser missense_variant 3/8 ENST00000298296.1 NP_619647.1 Q8TD91-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAGEC3ENST00000298296.1 linkuse as main transcriptc.497G>C p.Trp166Ser missense_variant 3/81 NM_138702.1 ENSP00000298296.1 Q8TD91-1

Frequencies

GnomAD3 genomes
AF:
0.0000817
AC:
9
AN:
110159
Hom.:
0
Cov.:
21
AF XY:
0.000123
AC XY:
4
AN XY:
32453
show subpopulations
Gnomad AFR
AF:
0.000233
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000290
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000190
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000441
AC:
6
AN:
136168
Hom.:
0
AF XY:
0.0000245
AC XY:
1
AN XY:
40742
show subpopulations
Gnomad AFR exome
AF:
0.000429
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000939
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000561
AC:
6
AN:
1069383
Hom.:
0
Cov.:
32
AF XY:
0.00000578
AC XY:
2
AN XY:
345933
show subpopulations
Gnomad4 AFR exome
AF:
0.0000777
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:
0.00000484
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000817
AC:
9
AN:
110210
Hom.:
0
Cov.:
21
AF XY:
0.000123
AC XY:
4
AN XY:
32514
show subpopulations
Gnomad4 AFR
AF:
0.000232
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000291
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000190
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000491
ExAC
AF:
0.0000342
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 16, 2023The c.497G>C (p.W166S) alteration is located in exon 3 (coding exon 3) of the MAGEC3 gene. This alteration results from a G to C substitution at nucleotide position 497, causing the tryptophan (W) at amino acid position 166 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
0.14
BayesDel_addAF
Benign
-0.66
T
BayesDel_noAF
Benign
-0.87
CADD
Benign
5.2
DANN
Benign
0.57
DEOGEN2
Benign
0.0040
T
FATHMM_MKL
Benign
0.039
N
LIST_S2
Benign
0.23
T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.040
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-0.060
N
REVEL
Benign
0.024
Sift
Benign
0.13
T
Sift4G
Pathogenic
0.0
D
Polyphen
0.62
P
Vest4
0.12
MVP
0.12
MPC
0.028
ClinPred
0.018
T
Varity_R
0.26
gMVP
0.051

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs140752145; hg19: chrX-140967199; API