X-152135332-C-T

Position:

chrX-152135332-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000370323.9(MAGEA10):c.289G>A(p.Val97Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000612 in 1,208,417 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 26 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000061 ( 0 hom. 25 hem. )

Consequence

MAGEA10
ENST00000370323.9 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.741

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03605032).

BP6

Variant X-152135332-C-T is Benign according to our data. Variant chrX-152135332-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2602054.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 25 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAGEA10	NM_021048.5 linkuse as main transcript	c.289G>A	p.Val97Ile	missense_variant	4/4	ENST00000370323.9	NP_066386.3
LOC100533997	NM_001204811.3 linkuse as main transcript	c.-278+3143G>A		intron_variant			NP_001191740.1
MAGEA10	NM_001011543.3 linkuse as main transcript	c.289G>A	p.Val97Ile	missense_variant	5/5		NP_001011543.3
MAGEA10	NM_001251828.2 linkuse as main transcript	c.289G>A	p.Val97Ile	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.289G>A	p.Val97Ile	missense_variant	4/4	1	NM_021048.5	ENSP00000359347	P1

Frequencies

GnomAD3 genomes

AF:

0.0000631

AC:

AN:

110947

Hom.:

Cov.:

AF XY:

0.0000302

AC XY:

AN XY:

33161

show subpopulations

Gnomad AFR

AF:

0.0000656

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000957

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:

0.0000756

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000220

AC:

AN:

182011

Hom.:

AF XY:

0.0000451

AC XY:

AN XY:

66545

show subpopulations

Gnomad AFR exome

AF:

0.0000761

Gnomad AMR exome

AF:

0.0000367

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:

0.0000123

Gnomad OTH exome

AF:

0.000223

GnomAD4 exome

AF:

0.0000611

AC:

AN:

1097417

Hom.:

Cov.:

AF XY:

0.0000689

AC XY:

AN XY:

362803

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000570

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000713

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000631

AC:

AN:

111000

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

AN XY:

33224

show subpopulations

Gnomad4 AFR

AF:

0.0000655

Gnomad4 AMR

AF:

0.0000956

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000756

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.010

DANN

Benign

0.60

DEOGEN2

Benign

0.0020

T;T;T;T

FATHMM_MKL

Benign

0.0052

LIST_S2

Benign

0.14

.;T;T;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.036

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.60

N;N;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.020

N;N;N;N

REVEL

Benign

0.0070

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;.;.

Polyphen

0.0

B;B;.;.

Vest4

0.031

MVP

0.14

MPC

0.065

ClinPred

0.042

GERP RS

-4.3

Varity_R

0.032

gMVP

0.046

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