Genetic Variant MAGEA10:p.Glu26Lys (chrX-152135545-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.76G>A(p.Glu26Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000699 in 1,159,106 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., 12 hem., cov: 23)

Exomes 𝑓: 0.000045 ( 0 hom. 14 hem. )

Consequence

MAGEA10
NM_021048.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.44

Publications

1 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=0.01250729).

BS2

High Hemizygotes in GnomAd4 at 12 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.76G>A	p.Glu26Lys	missense	Exon 4 of 4	NP_066386.3	P43363
MAGEA10	NM_001011543.3		c.76G>A	p.Glu26Lys	missense	Exon 5 of 5	NP_001011543.3	P43363
MAGEA10	NM_001251828.2		c.76G>A	p.Glu26Lys	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.76G>A	p.Glu26Lys	missense	Exon 4 of 4	ENSP00000359347.4	P43363
MAGEA10	ENST00000244096.7	TSL:2	c.76G>A	p.Glu26Lys	missense	Exon 5 of 5	ENSP00000244096.3	P43363
MAGEA10	ENST00000444834.6	TSL:3	c.76G>A	p.Glu26Lys	missense	Exon 5 of 5	ENSP00000406161.2	C9J958

Frequencies

GnomAD3 genomes

AF:

0.000295

AC:

AN:

112024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000128

AC:

AN:

140320

AF XY:

0.0000427

show subpopulations

Gnomad AFR exome

AF:

0.00114

Gnomad AMR exome

AF:

0.0000521

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000751

Gnomad NFE exome

AF:

0.0000304

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000449

AC:

AN:

1047031

Hom.:

Cov.:

AF XY:

0.0000417

AC XY:

AN XY:

335923

show subpopulations

African (AFR)

AF:

0.00107

AC:

AN:

24404

American (AMR)

AF:

0.0000379

AC:

AN:

26392

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15609

East Asian (EAS)

AF:

0.0000335

AC:

AN:

29849

South Asian (SAS)

AF:

0.00

AC:

AN:

45907

European-Finnish (FIN)

AF:

0.000104

AC:

AN:

38580

Middle Eastern (MID)

AF:

0.000517

AC:

AN:

3870

European-Non Finnish (NFE)

AF:

0.0000134

AC:

AN:

818608

Other (OTH)

AF:

0.0000456

AC:

AN:

43812

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.000303

AC:

AN:

112075

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

34251

show subpopulations

African (AFR)

AF:

0.00107

AC:

AN:

30884

American (AMR)

AF:

0.00

AC:

AN:

10665

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3525

South Asian (SAS)

AF:

0.00

AC:

AN:

2673

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6141

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53106

Other (OTH)

AF:

0.00

AC:

AN:

1533

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.557

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:

0.000214

Hom.:

Bravo

AF:

0.000389

ESP6500AA

AF:

0.00104

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000142

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

0.091

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.0

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.013

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.21

M_CAP

Benign

0.0047

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.77

PhyloP100

-1.4

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.84

REVEL

Benign

0.074

Sift

Benign

0.81

Sift4G

Benign

0.84

Polyphen

0.96

Vest4

0.044

MVP

0.12

MPC

0.21

ClinPred

0.050

GERP RS

-1.6

Varity_R

0.080

gMVP

0.13

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