X-152134624-C-A

Variant summary

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

The NM_021048.5(MAGEA10):​c.997G>T​(p.Ala333Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 21)

Consequence

MAGEA10
NM_021048.5 missense

Scores

2
4
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.725
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]

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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=0.38660753).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MAGEA10NM_021048.5 linkuse as main transcriptc.997G>T p.Ala333Ser missense_variant 4/4 ENST00000370323.9 NP_066386.3 P43363B2RAE8
MAGEA10NM_001011543.3 linkuse as main transcriptc.997G>T p.Ala333Ser missense_variant 5/5 NP_001011543.3 P43363B2RAE8
MAGEA10NM_001251828.2 linkuse as main transcriptc.997G>T p.Ala333Ser missense_variant 5/5 NP_001238757.2 P43363B2RAE8
LOC100533997NM_001204811.3 linkuse as main transcriptc.-278+3851G>T intron_variant NP_001191740.1 P43359

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAGEA10ENST00000370323.9 linkuse as main transcriptc.997G>T p.Ala333Ser missense_variant 4/41 NM_021048.5 ENSP00000359347.4 P43363

Frequencies

GnomAD3 genomes
Cov.:
21
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
21

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 GeneticsJan 26, 2022The c.997G>T (p.A333S) alteration is located in exon 5 (coding exon 1) of the MAGEA10 gene. This alteration results from a G to T substitution at nucleotide position 997, causing the alanine (A) at amino acid position 333 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
Uncertain
0.35
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.24
T;T
FATHMM_MKL
Benign
0.050
N
LIST_S2
Benign
0.82
.;T
M_CAP
Benign
0.0063
T
MetaRNN
Benign
0.39
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
3.2
M;M
PrimateAI
Benign
0.29
T
PROVEAN
Uncertain
-3.0
D;D
REVEL
Benign
0.047
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.0060
D;D
Polyphen
0.92
P;P
Vest4
0.21
MutPred
0.69
Gain of phosphorylation at A333 (P = 0.0187);Gain of phosphorylation at A333 (P = 0.0187);
MVP
0.39
MPC
0.40
ClinPred
0.99
D
GERP RS
1.7
Varity_R
0.38
gMVP
0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-151303096; API