chrX-51894771-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001005333.2(MAGED1):​c.190C>T​(p.Pro64Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000875 in 1,142,624 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 20)
Exomes 𝑓: 0.0000077 ( 0 hom. 1 hem. )

Consequence

MAGED1
NM_001005333.2 missense

Scores

14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03
Variant links:
Genes affected
MAGED1 (HGNC:6813): (MAGE family member D1) This gene is a member of the melanoma antigen gene (MAGE) family. Most of the genes of this family encode tumor specific antigens that are not expressed in normal adult tissues except testis. Although the protein encoded by this gene shares strong homology with members of the MAGE family, it is expressed in almost all normal adult tissues. This gene has been demonstrated to be involved in the p75 neurotrophin receptor mediated programmed cell death pathway. Three transcript variants encoding two different 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 Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.09118655).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAGED1NM_006986.4 linkc.46-282C>T intron_variant Intron 2 of 12 ENST00000326587.12 NP_008917.3 Q9Y5V3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAGED1ENST00000326587.12 linkc.46-282C>T intron_variant Intron 2 of 12 1 NM_006986.4 ENSP00000325333.8 Q9Y5V3-1

Frequencies

GnomAD3 genomes
AF:
0.0000184
AC:
2
AN:
108895
Hom.:
0
Cov.:
20
AF XY:
0.0000321
AC XY:
1
AN XY:
31185
show subpopulations
Gnomad AFR
AF:
0.0000336
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:
0.0000191
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000777
AC:
1
AN:
128653
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
43285
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:
0.0000161
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000774
AC:
8
AN:
1033729
Hom.:
0
Cov.:
32
AF XY:
0.00000301
AC XY:
1
AN XY:
332733
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:
0.00000982
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000184
AC:
2
AN:
108895
Hom.:
0
Cov.:
20
AF XY:
0.0000321
AC XY:
1
AN XY:
31185
show subpopulations
Gnomad4 AFR
AF:
0.0000336
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:
0.0000191
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000142
Hom.:
1
Bravo
AF:
0.00000378
ExAC
AF:
0.00000838
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 09, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.190C>T (p.P64S) alteration is located in exon 3 (coding exon 2) of the MAGED1 gene. This alteration results from a C to T substitution at nucleotide position 190, causing the proline (P) at amino acid position 64 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
BayesDel_addAF
Benign
-0.52
T
BayesDel_noAF
Benign
-0.97
CADD
Benign
12
DANN
Benign
0.92
FATHMM_MKL
Benign
0.085
N
LIST_S2
Benign
0.41
T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.091
T
MetaSVM
Benign
-0.97
T
PrimateAI
Benign
0.28
T
PROVEAN
Benign
0.22
N
REVEL
Benign
0.053
Sift
Benign
0.20
T
Sift4G
Benign
0.12
T
Polyphen
0.18
B
Vest4
0.34
MutPred
0.33
Gain of catalytic residue at P64 (P = 0.0016);
MVP
0.12
MPC
0.078
ClinPred
0.074
T
GERP RS
3.2
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs782185908; hg19: chrX-51637867; API