X-152135220-A-T

Variant summary

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

The NM_021048.5(MAGEA10):​c.401T>A​(p.Ile134Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I134T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 22)
Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )
Failed GnomAD Quality Control

Consequence

MAGEA10
NM_021048.5 missense

Scores

1
4
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.203
Variant links:
Genes affected
MAGEA10 (HGNC:6797): (MAGE family member A10) This gene is a member of the MAGEA gene family. The members of this family encode proteins with 50 to 80% sequence identity to each other. The promoters and first exons of the MAGEA genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. The MAGEA genes are clustered at chromosomal location Xq28. They have been implicated in some hereditary disorders, such as dyskeratosis congenita. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream melanoma antigen family A, 5 (MAGEA5) gene.[provided by RefSeq, Oct 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=0.281413).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAGEA10NM_021048.5 linkc.401T>A p.Ile134Lys missense_variant Exon 4 of 4 ENST00000370323.9 NP_066386.3 P43363B2RAE8
MAGEA10NM_001011543.3 linkc.401T>A p.Ile134Lys missense_variant Exon 5 of 5 NP_001011543.3 P43363B2RAE8
MAGEA10NM_001251828.2 linkc.401T>A p.Ile134Lys missense_variant Exon 5 of 5 NP_001238757.2 P43363B2RAE8
LOC100533997NM_001204811.3 linkc.-278+3255T>A intron_variant Intron 1 of 3 NP_001191740.1 P43359

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAGEA10ENST00000370323.9 linkc.401T>A p.Ile134Lys missense_variant Exon 4 of 4 1 NM_021048.5 ENSP00000359347.4 P43363

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD3 exomes
AF:
0.00000552
AC:
1
AN:
181113
Hom.:
0
AF XY:
0.0000152
AC XY:
1
AN XY:
65665
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:
0.0000544
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
9.12e-7
AC:
1
AN:
1096334
Hom.:
0
Cov.:
32
AF XY:
0.00000276
AC XY:
1
AN XY:
361840
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:
0.0000186
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
14
DANN
Benign
0.76
DEOGEN2
Benign
0.16
T;T;T;T
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.11
.;T;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.28
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.5
M;M;.;.
PrimateAI
Uncertain
0.48
T
PROVEAN
Pathogenic
-5.1
D;D;D;D
REVEL
Benign
0.13
Sift
Uncertain
0.0020
D;D;D;D
Sift4G
Uncertain
0.0020
D;D;.;.
Polyphen
0.61
P;P;.;.
Vest4
0.58
MutPred
0.65
Gain of ubiquitination at I134 (P = 0.0048);Gain of ubiquitination at I134 (P = 0.0048);Gain of ubiquitination at I134 (P = 0.0048);Gain of ubiquitination at I134 (P = 0.0048);
MVP
0.22
MPC
0.39
ClinPred
0.31
T
GERP RS
1.4
Varity_R
0.61
gMVP
0.62

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: rs377180452; hg19: chrX-151303692; API