X-152135337-G-A

Position:

chrX-152135337-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000370323.9(MAGEA10):c.284C>T(p.Ser95Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,208,496 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000036 ( 0 hom. 1 hem. )

Consequence

MAGEA10
ENST00000370323.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.15

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]

MAGEA10 links:

LOC100533997 (HGNC:):

LOC100533997 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04347253).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAGEA10	NM_021048.5 linkuse as main transcript	c.284C>T	p.Ser95Leu	missense_variant	4/4	ENST00000370323.9	NP_066386.3
LOC100533997	NM_001204811.3 linkuse as main transcript	c.-278+3138C>T		intron_variant			NP_001191740.1
MAGEA10	NM_001011543.3 linkuse as main transcript	c.284C>T	p.Ser95Leu	missense_variant	5/5		NP_001011543.3
MAGEA10	NM_001251828.2 linkuse as main transcript	c.284C>T	p.Ser95Leu	missense_variant	5/5		NP_001238757.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEA10	ENST00000370323.9 linkuse as main transcript	c.284C>T	p.Ser95Leu	missense_variant	4/4	1	NM_021048.5	ENSP00000359347	P1

Frequencies

GnomAD3 genomes

AF:

0.00000900

AC:

AN:

111132

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33296

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000330

AC:

AN:

181651

Hom.:

AF XY:

0.0000453

AC XY:

AN XY:

66193

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000367

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000535

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000494

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000365

AC:

AN:

1097313

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

362715

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000285

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:

0.00000356

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000899

AC:

AN:

111183

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33357

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000189

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000577

AC:

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 submitter

clinical testing

Ambry Genetics

Jun 03, 2022

The c.284C>T (p.S95L) alteration is located in exon 5 (coding exon 1) of the MAGEA10 gene. This alteration results from a C to T substitution at nucleotide position 284, causing the serine (S) at amino acid position 95 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

0.082

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.5

DANN

Benign

0.59

DEOGEN2

Benign

0.025

T;T;T;T

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.20

.;T;T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.043

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.4

M;M;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-2.1

N;N;N;N

REVEL

Benign

0.040

Sift

Benign

0.040

D;D;D;D

Sift4G

Benign

0.064

T;T;.;.

Polyphen

0.15

B;B;.;.

Vest4

0.020

MutPred

0.23

Loss of phosphorylation at S95 (P = 0.0187);Loss of phosphorylation at S95 (P = 0.0187);Loss of phosphorylation at S95 (P = 0.0187);Loss of phosphorylation at S95 (P = 0.0187);

MVP

0.11

MPC

0.083

ClinPred

0.073

GERP RS

-0.96

Varity_R

0.058

gMVP

0.13

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over