X-141905831-A-C

Variant summary

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

The NM_005462.5(MAGEC1):ā€‹c.427A>Cā€‹(p.Ile143Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,203,325 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000072 ( 0 hom., 3 hem., cov: 24)
Exomes š‘“: 0.000030 ( 0 hom. 11 hem. )

Consequence

MAGEC1
NM_005462.5 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.39
Variant links:
Genes affected
MAGEC1 (HGNC:6812): (MAGE family member C1) This gene is a member of the melanoma antigen gene (MAGE) family. The proteins of this family are tumor-specific antigens that can be recognized by autologous cytolytic T lymphocytes. This protein contains a large number of unique short repetitive sequences in front of the MAGE-homologous sequence, and therefore is about 800 aa longer than the other MAGE proteins. [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=0.027721047).
BS2
High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MAGEC1NM_005462.5 linkuse as main transcriptc.427A>C p.Ile143Leu missense_variant 4/4 ENST00000285879.5 NP_005453.2
MAGEC1XM_011531418.3 linkuse as main transcriptc.427A>C p.Ile143Leu missense_variant 4/4 XP_011529720.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAGEC1ENST00000285879.5 linkuse as main transcriptc.427A>C p.Ile143Leu missense_variant 4/41 NM_005462.5 ENSP00000285879 P3O60732-1
MAGEC1ENST00000406005.2 linkuse as main transcriptc.-115+284A>C intron_variant 1 ENSP00000385500 A2O60732-2

Frequencies

GnomAD3 genomes
AF:
0.0000718
AC:
8
AN:
111386
Hom.:
0
Cov.:
24
AF XY:
0.0000882
AC XY:
3
AN XY:
34014
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000284
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000373
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000566
Gnomad OTH
AF:
0.000669
GnomAD3 exomes
AF:
0.0000497
AC:
9
AN:
181139
Hom.:
0
AF XY:
0.0000448
AC XY:
3
AN XY:
66955
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000110
Gnomad ASJ exome
AF:
0.000134
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000662
Gnomad NFE exome
AF:
0.0000492
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000302
AC:
33
AN:
1091939
Hom.:
0
Cov.:
36
AF XY:
0.0000303
AC XY:
11
AN XY:
363265
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000144
Gnomad4 ASJ exome
AF:
0.0000520
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000502
Gnomad4 NFE exome
AF:
0.0000274
Gnomad4 OTH exome
AF:
0.0000437
GnomAD4 genome
AF:
0.0000718
AC:
8
AN:
111386
Hom.:
0
Cov.:
24
AF XY:
0.0000882
AC XY:
3
AN XY:
34014
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000284
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000373
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000566
Gnomad4 OTH
AF:
0.000669
ExAC
AF:
0.0000666
AC:
8

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 GeneticsDec 14, 2023The c.427A>C (p.I143L) alteration is located in exon 4 (coding exon 2) of the MAGEC1 gene. This alteration results from a A to C substitution at nucleotide position 427, causing the isoleucine (I) at amino acid position 143 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
0.13
BayesDel_addAF
Benign
-0.68
T
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.0090
DANN
Benign
0.62
DEOGEN2
Benign
0.0035
T
FATHMM_MKL
Benign
0.0055
N
LIST_S2
Benign
0.19
T
M_CAP
Benign
0.0027
T
MetaRNN
Benign
0.028
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
-0.55
N
MutationTaster
Benign
1.0
D;N
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
0.020
N
REVEL
Benign
0.0090
Sift
Benign
0.28
T
Sift4G
Benign
0.42
T
Polyphen
0.0010
B
Vest4
0.047
MVP
0.076
ClinPred
0.038
T
Varity_R
0.17
gMVP
0.0086

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: rs752350196; hg19: chrX-140993617; API