Genetic Variant MAGEA10:p.Arg293Gln (chrX-152134743-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_021048.5(MAGEA10):c.878G>A(p.Arg293Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000024 in 1,209,223 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 1 hem., cov: 21)

Exomes 𝑓: 0.000021 ( 0 hom. 10 hem. )

Consequence

MAGEA10
NM_021048.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.06

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022757411).

BS2

High Hemizygotes in GnomAdExome4 at 10 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021048.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAGEA10	NM_021048.5	MANE Select	c.878G>A	p.Arg293Gln	missense	Exon 4 of 4	NP_066386.3	P43363
MAGEA10	NM_001011543.3		c.878G>A	p.Arg293Gln	missense	Exon 5 of 5	NP_001011543.3	P43363
MAGEA10	NM_001251828.2		c.878G>A	p.Arg293Gln	missense	Exon 5 of 5	NP_001238757.2	P43363

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAGEA10	ENST00000370323.9	TSL:1 MANE Select	c.878G>A	p.Arg293Gln	missense	Exon 4 of 4	ENSP00000359347.4	P43363
MAGEA10	ENST00000244096.7	TSL:2	c.878G>A	p.Arg293Gln	missense	Exon 5 of 5	ENSP00000244096.3	P43363
ENSG00000266560	ENST00000509345.6	TSL:4	n.47+3732G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000540

AC:

AN:

111088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000284

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000754

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000109

AC:

AN:

183519

AF XY:

0.000206

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000866

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000610

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.0000209

AC:

AN:

1098135

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

363493

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26400

American (AMR)

AF:

0.0000568

AC:

AN:

35206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19385

East Asian (EAS)

AF:

0.000232

AC:

AN:

30206

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54147

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40531

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.0000131

AC:

AN:

842029

Other (OTH)

AF:

0.0000434

AC:

AN:

46095

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000540

AC:

AN:

111088

Hom.:

Cov.:

AF XY:

0.0000301

AC XY:

AN XY:

33270

show subpopulations

African (AFR)

AF:

0.0000328

AC:

AN:

30502

American (AMR)

AF:

0.00

AC:

AN:

10497

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2638

East Asian (EAS)

AF:

0.000284

AC:

AN:

3515

South Asian (SAS)

AF:

0.00

AC:

AN:

2561

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5931

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.0000754

AC:

AN:

53021

Other (OTH)

AF:

0.00

AC:

AN:

1496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.000140

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.46

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.017

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.14

M_CAP

Benign

0.0066

MetaRNN

Benign

0.023

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.7

PhyloP100

-1.1

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.017

Sift

Benign

0.40

Sift4G

Benign

0.47

Polyphen

0.28

Vest4

0.014

MVP

0.19

MPC

0.11

ClinPred

0.013

GERP RS

-0.38

Varity_R

0.064

gMVP

0.22

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over