X-152134536-G-A

Position:

chrX-152134536-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000370323.9(MAGEA10):c.1085C>T(p.Thr362Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000606 in 1,205,119 control chromosomes in the GnomAD database, including 1 homozygotes. There are 21 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., 1 hem., cov: 21)

Exomes 𝑓: 0.000062 ( 1 hom. 20 hem. )

Consequence

MAGEA10
ENST00000370323.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.186

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08175179).

BS2

High Hemizygotes in GnomAdExome4 at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAGEA10	NM_021048.5 linkuse as main transcript	c.1085C>T	p.Thr362Ile	missense_variant	4/4	ENST00000370323.9	NP_066386.3
LOC100533997	NM_001204811.3 linkuse as main transcript	c.-278+3939C>T		intron_variant			NP_001191740.1
MAGEA10	NM_001011543.3 linkuse as main transcript	c.1085C>T	p.Thr362Ile	missense_variant	5/5		NP_001011543.3
MAGEA10	NM_001251828.2 linkuse as main transcript	c.1085C>T	p.Thr362Ile	missense_variant	5/5		NP_001238757.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MAGEA10	ENST00000370323.9 linkuse as main transcript	c.1085C>T	p.Thr362Ile	missense_variant	4/4	1	NM_021048.5	ENSP00000359347	P1
MAGEA10	ENST00000244096.7 linkuse as main transcript	c.1085C>T	p.Thr362Ile	missense_variant	5/5	2		ENSP00000244096	P1
	ENST00000577437.1 linkuse as main transcript	n.469+1027C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000458

AC:

AN:

109053

Hom.:

Cov.:

AF XY:

0.0000317

AC XY:

AN XY:

31517

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:

0.0000760

Gnomad OTH

AF:

0.000684

GnomAD3 exomes

AF:

0.0000549

AC:

AN:

182303

Hom.:

AF XY:

0.0000299

AC XY:

AN XY:

66835

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000366

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:

0.000111

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000620

AC:

AN:

1096020

Hom.:

Cov.:

AF XY:

0.0000553

AC XY:

AN XY:

361476

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000994

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000690

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000458

AC:

AN:

109099

Hom.:

Cov.:

AF XY:

0.0000317

AC XY:

AN XY:

31573

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:

0.0000760

Gnomad4 OTH

AF:

0.000676

Alfa

AF:

0.000327

Hom.:

Bravo

AF:

0.0000416

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000494

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

Oct 05, 2021

The c.1085C>T (p.T362I) 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 1085, causing the threonine (T) at amino acid position 362 to be replaced by an isoleucine (I). 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

0.14

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.7

DANN

Benign

0.72

DEOGEN2

Benign

0.021

T;T

FATHMM_MKL

Benign

0.0087

LIST_S2

Benign

0.26

.;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.082

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.0

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.011

Sift

Benign

0.043

D;D

Sift4G

Benign

0.072

T;T

Polyphen

0.027

B;B

Vest4

0.070

MutPred

0.23

Loss of glycosylation at T362 (P = 0.0081);Loss of glycosylation at T362 (P = 0.0081);

MVP

0.25

MPC

0.089

ClinPred

0.024

GERP RS

-1.3

Varity_R

0.067

gMVP

0.18

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.

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