Genetic Variant MAGEA10:p.Met354Ile (chrX-152134559-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021048.5(MAGEA10):c.1062G>A(p.Met354Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000183 in 1,095,681 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: not found (cov: 21)

Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

MAGEA10
NM_021048.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.160

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045247287).

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.1062G>A	p.Met354Ile	missense	Exon 4 of 4	NP_066386.3	P43363
MAGEA10	NM_001011543.3		c.1062G>A	p.Met354Ile	missense	Exon 5 of 5	NP_001011543.3	P43363
MAGEA10	NM_001251828.2		c.1062G>A	p.Met354Ile	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.1062G>A	p.Met354Ile	missense	Exon 4 of 4	ENSP00000359347.4	P43363
MAGEA10	ENST00000244096.7	TSL:2	c.1062G>A	p.Met354Ile	missense	Exon 5 of 5	ENSP00000244096.3	P43363
ENSG00000266560	ENST00000509345.6	TSL:4	n.47+3916G>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000109

AC:

AN:

183313

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000729

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000183

AC:

AN:

1095681

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

361075

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26362

American (AMR)

AF:

0.0000568

AC:

AN:

35205

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19362

East Asian (EAS)

AF:

0.00

AC:

AN:

30192

South Asian (SAS)

AF:

0.00

AC:

AN:

54077

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40531

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4121

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

839824

Other (OTH)

AF:

0.00

AC:

AN:

46007

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Cov.:

Alfa

AF:

0.00

Hom.:

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

0.31

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.94

CADD

Benign

3.5

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.025

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.23

M_CAP

Benign

0.0042

MetaRNN

Benign

0.045

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.5

PhyloP100

0.16

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.5

REVEL

Benign

0.012

Sift

Benign

0.18

Sift4G

Benign

0.25

Polyphen

0.0

Vest4

0.14

MutPred

0.26

Gain of sheet (P = 0.0221)

MVP

0.33

MPC

0.087

ClinPred

0.018

GERP RS

-0.19

Varity_R

0.13

gMVP

0.14

Mutation Taster

=99/1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over