X-152135220-A-G

Position:

chrX-152135220-A-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_021048.5(MAGEA10):c.401T>C(p.Ile134Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,207,961 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 67 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.00017 ( 0 hom. 65 hem. )

Consequence

MAGEA10
NM_021048.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

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]

MAGEA10 links:

LOC100533997 (HGNC:):

LOC100533997 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.076803535).

BP6

Variant X-152135220-A-G is Benign according to our data. Variant chrX-152135220-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2460568.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEA10	NM_021048.5 linkuse as main transcript	c.401T>C	p.Ile134Thr	missense_variant	4/4	ENST00000370323.9	NP_066386.3	P43363B2RAE8
MAGEA10	NM_001011543.3 linkuse as main transcript	c.401T>C	p.Ile134Thr	missense_variant	5/5		NP_001011543.3	P43363B2RAE8
MAGEA10	NM_001251828.2 linkuse as main transcript	c.401T>C	p.Ile134Thr	missense_variant	5/5		NP_001238757.2	P43363B2RAE8
LOC100533997	NM_001204811.3 linkuse as main transcript	c.-278+3255T>C		intron_variant			NP_001191740.1	P43359

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEA10	ENST00000370323.9 linkuse as main transcript	c.401T>C	p.Ile134Thr	missense_variant	4/4	1	NM_021048.5	ENSP00000359347.4		P43363

Frequencies

GnomAD3 genomes

AF:

0.000134

AC:

AN:

111627

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

33817

show subpopulations

Gnomad AFR

AF:

0.0000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000947

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000326

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000133

AC:

AN:

181113

Hom.:

AF XY:

0.0000305

AC XY:

AN XY:

65665

show subpopulations

Gnomad AFR exome

AF:

0.0000761

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:

0.000569

Gnomad NFE exome

AF:

0.000173

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000173

AC:

190

AN:

1096334

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

AN XY:

361840

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

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:

0.000494

Gnomad4 NFE exome

AF:

0.000197

Gnomad4 OTH exome

AF:

0.0000652

GnomAD4 genome

AF:

0.000134

AC:

AN:

111627

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

33817

show subpopulations

Gnomad4 AFR

AF:

0.0000652

Gnomad4 AMR

AF:

0.0000947

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000326

Gnomad4 NFE

AF:

0.000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000324

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.401T>C (p.I134T) alteration is located in exon 5 (coding exon 1) of the MAGEA10 gene. This alteration results from a T to C substitution at nucleotide position 401, causing the isoleucine (I) at amino acid position 134 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

MAGEA10: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.15

T;T;T;T

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.12

.;T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.077

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.9

M;M;.;.

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.7

D;D;D;D

REVEL

Benign

0.054

Sift

Uncertain

0.0050

D;D;D;D

Sift4G

Uncertain

0.0050

D;D;.;.

Polyphen

0.94

P;P;.;.

Vest4

0.38

MVP

0.35

MPC

0.48

ClinPred

0.15

GERP RS

1.4

Varity_R

0.62

gMVP

0.25

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