Genetic Variant MAGEA8:p.Gln5Glu (chrX-149884285-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005364.5(MAGEA8):c.13C>G(p.Gln5Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 1,190,597 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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 0.000062 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.0000074 ( 0 hom. 1 hem. )

Consequence

MAGEA8
NM_005364.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.46

Publications

0 publications found

Variant links:

Genes affected

MAGEA8 (HGNC:6806): (MAGE family member A8) 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. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Oct 2009]

MAGEA8 links:

MAGEA8-AS1 (HGNC:45093): (MAGEA8 antisense RNA 1)

MAGEA8-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.078062385).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005364.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAGEA8	NM_005364.5	MANE Select	c.13C>G	p.Gln5Glu	missense	Exon 3 of 3	NP_005355.2
MAGEA8	NM_001166400.2		c.13C>G	p.Gln5Glu	missense	Exon 4 of 4	NP_001159872.1	P43361
MAGEA8	NM_001166401.2		c.13C>G	p.Gln5Glu	missense	Exon 3 of 3	NP_001159873.1	P43361

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAGEA8	ENST00000286482.6	TSL:1 MANE Select	c.13C>G	p.Gln5Glu	missense	Exon 3 of 3	ENSP00000286482.1	P43361
MAGEA8	ENST00000535454.5	TSL:3	c.13C>G	p.Gln5Glu	missense	Exon 4 of 4	ENSP00000438293.1	P43361
MAGEA8	ENST00000542674.5	TSL:3	c.13C>G	p.Gln5Glu	missense	Exon 3 of 3	ENSP00000443776.1	P43361

Frequencies

GnomAD3 genomes

AF:

0.0000622

AC:

AN:

112561

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000226

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000127

AC:

AN:

157497

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000159

Gnomad AMR exome

AF:

0.00

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:

0.00000742

AC:

AN:

1078036

Hom.:

Cov.:

AF XY:

0.00000287

AC XY:

AN XY:

349006

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

26036

American (AMR)

AF:

0.00

AC:

AN:

33313

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17833

East Asian (EAS)

AF:

0.00

AC:

AN:

30127

South Asian (SAS)

AF:

0.00

AC:

AN:

50244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39577

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3992

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

831642

Other (OTH)

AF:

0.0000221

AC:

AN:

45272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

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:

0.0000622

AC:

AN:

112561

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

34705

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000226

AC:

AN:

31005

American (AMR)

AF:

0.00

AC:

AN:

10695

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3586

South Asian (SAS)

AF:

0.00

AC:

AN:

2739

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53235

Other (OTH)

AF:

0.00

AC:

AN:

1515

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000884173), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000604

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000825

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

0.073

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.41

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.011

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.24

M_CAP

Benign

0.00058

MetaRNN

Benign

0.078

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.1

PhyloP100

-1.5

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.1

REVEL

Benign

0.047

Sift

Uncertain

0.022

Sift4G

Benign

0.083

Polyphen

0.15

Vest4

0.15

MVP

0.11

MPC

0.35

ClinPred

0.051

GERP RS

-2.0

Varity_R

0.11

gMVP

0.33

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