dbSNP rs782082976: MAGEE1:p.Thr167Ala (chrX-76428429-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_020932.3(MAGEE1):c.499A>G(p.Thr167Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000489 in 1,207,268 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., 1 hem., cov: 26)

Exomes 𝑓: 0.000046 ( 0 hom. 19 hem. )

Consequence

MAGEE1
NM_020932.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.835

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04413283).

BS2

High Hemizygotes in GnomAdExome4 at 19 gene

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.499A>G	p.Thr167Ala	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.499A>G	p.Thr167Ala	missense	Exon 1 of 1	ENSP00000354912.2	Q9HCI5

Frequencies

GnomAD3 genomes

AF:

0.0000729

AC:

AN:

109810

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000153

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000555

AC:

AN:

180243

AF XY:

0.0000454

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:

0.000126

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000465

AC:

AN:

1097458

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

363292

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26396

American (AMR)

AF:

0.00

AC:

AN:

35193

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19372

East Asian (EAS)

AF:

0.00

AC:

AN:

30198

South Asian (SAS)

AF:

0.00

AC:

AN:

54136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40039

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.0000546

AC:

AN:

841907

Other (OTH)

AF:

0.000109

AC:

AN:

46080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

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:

0.0000729

AC:

AN:

109810

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

33004

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29963

American (AMR)

AF:

0.00

AC:

AN:

10588

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2619

East Asian (EAS)

AF:

0.00

AC:

AN:

3423

South Asian (SAS)

AF:

0.00

AC:

AN:

2575

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5907

Middle Eastern (MID)

AF:

0.00

AC:

AN:

225

European-Non Finnish (NFE)

AF:

0.000153

AC:

AN:

52352

Other (OTH)

AF:

0.00

AC:

AN:

1492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

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:

0.000169

Hom.:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

0.078

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.96

CADD

Benign

(source)

DANN

Benign

0.36

DEOGEN2

Benign

0.016

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.31

M_CAP

Benign

0.0061

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.9

PhyloP100

-0.83

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.030

REVEL

Benign

0.082

Sift

Uncertain

0.011

Sift4G

Benign

0.19

Polyphen

0.0010

Vest4

0.053

MutPred

0.16

Loss of glycosylation at T167 (P = 0.0045)

MVP

0.043

MPC

0.31

ClinPred

0.064

GERP RS

-4.1

Varity_R

0.051

gMVP

0.27

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