Genetic Variant MAGEE1:p.Pro261Gln (chrX-76428712-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020932.3(MAGEE1):c.782C>A(p.Pro261Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000746 in 1,206,730 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 0.000036 ( 0 hom., 1 hem., cov: 26)

Exomes 𝑓: 0.0000046 ( 0 hom. 1 hem. )

Consequence

MAGEE1
NM_020932.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.43

Publications

1 publications found

Variant links:

Genes affected

MAGEE1 (HGNC:24934): (MAGE family member E1) This gene encodes an alpha-dystrobrevin-associated MAGE (melanoma-associated antigen) protein, which is a member of the MAGE family. The protein contains a nuclear localization signal in the N-terminus, 30 12-amino acid repeats beginning at nt 60 with the consensus sequence ASEGPSTSVLPT, and two MAGE domains in the C-terminus. It may play a signaling role in brain, muscle, and peripheral nerve. This gene is located on X chromosome in a region containing loci linked to cognitive disability. [provided by RefSeq, Mar 2010]

MAGEE1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.050031364).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020932.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEE1	NM_020932.3	MANE Select	c.782C>A	p.Pro261Gln	missense	Exon 1 of 1	NP_065983.1	Q9HCI5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEE1	ENST00000361470.4	TSL:6 MANE Select	c.782C>A	p.Pro261Gln	missense	Exon 1 of 1	ENSP00000354912.2	Q9HCI5

Frequencies

GnomAD3 genomes

AF:

0.0000364

AC:

AN:

109841

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000996

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:

0.0000192

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000222

AC:

AN:

180379

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000292

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000456

AC:

AN:

1096889

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363073

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26384

American (AMR)

AF:

0.00

AC:

AN:

35072

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19345

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30179

South Asian (SAS)

AF:

0.00

AC:

AN:

54096

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39843

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

841795

Other (OTH)

AF:

0.0000217

AC:

AN:

46039

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

AF:

0.0000364

AC:

AN:

109841

Hom.:

Cov.:

AF XY:

0.0000302

AC XY:

AN XY:

33061

show subpopulations

African (AFR)

AF:

0.0000996

AC:

AN:

30108

American (AMR)

AF:

0.00

AC:

AN:

10583

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2615

East Asian (EAS)

AF:

0.00

AC:

AN:

3417

South Asian (SAS)

AF:

0.00

AC:

AN:

2634

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5954

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000192

AC:

AN:

52141

Other (OTH)

AF:

0.00

AC:

AN:

1505

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.00

Hom.:

ExAC

AF:

0.0000247

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

-0.79

BayesDel_noAF

Benign

-1.1

CADD

Benign

4.1

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.018

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.32

M_CAP

Benign

0.024

MetaRNN

Benign

0.050

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.2

PhyloP100

-3.4

PrimateAI

Benign

0.22

PROVEAN

Benign

0.31

REVEL

Benign

0.025

Sift

Benign

0.099

Sift4G

Uncertain

0.048

Polyphen

0.57

Vest4

0.068

MutPred

0.20

Loss of glycosylation at S259 (P = 0.0891)

MVP

0.043

MPC

0.91

ClinPred

0.12

GERP RS

-2.2

Varity_R

0.034

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

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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