X-152135601-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021048.5(MAGEA10):c.20G>A(p.Arg7His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000784 in 1,135,595 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 28 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R7C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 5 hem., cov: 23)

Exomes 𝑓: 0.000074 ( 0 hom. 23 hem. )

Consequence

MAGEA10
NM_021048.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.489

Publications

6 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03603977).

BP6

Variant X-152135601-C-T is Benign according to our data. Variant chrX-152135601-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2661666.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 5 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.20G>A	p.Arg7His	missense	Exon 4 of 4	NP_066386.3	P43363
MAGEA10	NM_001011543.3		c.20G>A	p.Arg7His	missense	Exon 5 of 5	NP_001011543.3	P43363
MAGEA10	NM_001251828.2		c.20G>A	p.Arg7His	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.20G>A	p.Arg7His	missense	Exon 4 of 4	ENSP00000359347.4	P43363
MAGEA10	ENST00000244096.7	TSL:2	c.20G>A	p.Arg7His	missense	Exon 5 of 5	ENSP00000244096.3	P43363
MAGEA10	ENST00000444834.6	TSL:3	c.20G>A	p.Arg7His	missense	Exon 5 of 5	ENSP00000406161.2	C9J958

Frequencies

GnomAD3 genomes

AF:

0.000116

AC:

AN:

112312

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000936

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000370

Gnomad FIN

AF:

0.000969

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000752

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000846

AC:

AN:

130004

AF XY:

0.000112

show subpopulations

Gnomad AFR exome

AF:

0.0000829

Gnomad AMR exome

AF:

0.0000610

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000319

Gnomad NFE exome

AF:

0.0000805

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000743

AC:

AN:

1023232

Hom.:

Cov.:

AF XY:

0.0000707

AC XY:

AN XY:

325164

show subpopulations

African (AFR)

AF:

0.000338

AC:

AN:

23698

American (AMR)

AF:

0.0000433

AC:

AN:

23103

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14667

East Asian (EAS)

AF:

0.0000338

AC:

AN:

29548

South Asian (SAS)

AF:

0.0000241

AC:

AN:

41545

European-Finnish (FIN)

AF:

0.000346

AC:

AN:

37621

Middle Eastern (MID)

AF:

0.000264

AC:

AN:

3783

European-Non Finnish (NFE)

AF:

0.0000608

AC:

AN:

806488

Other (OTH)

AF:

0.0000468

AC:

AN:

42779

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

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:

0.000116

AC:

AN:

112363

Hom.:

Cov.:

AF XY:

0.000145

AC XY:

AN XY:

34521

show subpopulations

African (AFR)

AF:

0.0000323

AC:

AN:

30955

American (AMR)

AF:

0.0000935

AC:

AN:

10694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3536

South Asian (SAS)

AF:

0.000371

AC:

AN:

2693

European-Finnish (FIN)

AF:

0.000969

AC:

AN:

6192

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.0000752

AC:

AN:

53197

Other (OTH)

AF:

0.00

AC:

AN:

1548

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.0000453

Hom.:

Bravo

AF:

0.0000340

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000952

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.1

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0077

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.62

M_CAP

Benign

0.0057

MetaRNN

Benign

0.036

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

PhyloP100

0.49

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.62

REVEL

Benign

0.067

Sift

Benign

0.23

Sift4G

Benign

0.18

Polyphen

0.42

Vest4

0.20

MVP

0.38

MPC

0.48

ClinPred

0.043

GERP RS

0.55

Varity_R

0.034

gMVP

0.12

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