Genetic Variant MAGEE2:p.Glu385Gln (chrX-75783899-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138703.5(MAGEE2):c.1153G>C(p.Glu385Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,098,103 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Consequence

MAGEE2
NM_138703.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.33

Publications

0 publications found

Variant links:

Genes affected

MAGEE2 (HGNC:24935): (MAGE family member E2) This gene encodes a member of the E subfamily of MAGE (melanoma antigen-encoding gene) gene family. The gene is intronless and the encoded protein has two of the MAGE domains which are characteristic of MAGE family proteins. [provided by RefSeq, Sep 2011]

MAGEE2 Gene-Disease associations (from GenCC):

male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: XL Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

MAGEE2 links:

LOC107985664 (HGNC:):

LOC107985664 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21073568).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138703.5. 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
	MAGEE2	NM_138703.5	MANE Select	c.1153G>C	p.Glu385Gln	missense	Exon 1 of 1	NP_619648.1	Q8TD90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEE2	ENST00000373359.4	TSL:6 MANE Select	c.1153G>C	p.Glu385Gln	missense	Exon 1 of 1	ENSP00000362457.2	Q8TD90

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000164

AC:

AN:

183131

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.00000182

AC:

AN:

1098103

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363467

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26401

American (AMR)

AF:

0.00

AC:

AN:

35203

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19380

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54147

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

842048

Other (OTH)

AF:

0.0000217

AC:

AN:

46093

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

ExAC

AF:

0.0000330

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

0.14

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0096

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.62

M_CAP

Benign

0.0061

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

2.3

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.0

REVEL

Benign

0.046

Sift

Benign

0.034

Sift4G

Benign

0.091

Polyphen

1.0

Vest4

0.062

MutPred

0.35

Loss of glycosylation at P384 (P = 0.1141)

MVP

0.31

MPC

0.083

ClinPred

0.40

GERP RS

2.8

Varity_R

0.22

gMVP

0.29

Mutation Taster

=97/3

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over