Variant X-75784065-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_138703.5(MAGEE2):c.987G>A(p.Met329Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0021 in 1,208,479 control chromosomes in the GnomAD database, including 2 homozygotes. There are 796 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., 25 hem., cov: 22)

Exomes 𝑓: 0.0022 ( 2 hom. 771 hem. )

Consequence

MAGEE2
NM_138703.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.521

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 links:

LOC107985664 (HGNC:):

LOC107985664 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009828895).

BS2

High Hemizygotes in GnomAd4 at 25 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGEE2	NM_138703.5 linkuse as main transcript	c.987G>A	p.Met329Ile	missense_variant	1/1	ENST00000373359.4
LOC107985664	XR_007068273.1 linkuse as main transcript	n.822-7227C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGEE2	ENST00000373359.4 linkuse as main transcript	c.987G>A	p.Met329Ile	missense_variant	1/1		NM_138703.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00113

AC:

127

AN:

112332

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

AN XY:

34484

show subpopulations

Gnomad AFR

AF:

0.000453

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000281

Gnomad ASJ

AF:

0.00264

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00190

Gnomad OTH

AF:

0.00132

GnomAD3 exomes

AF:

0.000993

AC:

180

AN:

181329

Hom.:

AF XY:

0.000889

AC XY:

AN XY:

66371

show subpopulations

Gnomad AFR exome

AF:

0.000380

Gnomad AMR exome

AF:

0.0000729

Gnomad ASJ exome

AF:

0.00201

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000315

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00181

Gnomad OTH exome

AF:

0.000887

GnomAD4 exome

AF:

0.00219

AC:

2405

AN:

1096092

Hom.:

Cov.:

AF XY:

0.00213

AC XY:

771

AN XY:

362310

show subpopulations

Gnomad4 AFR exome

AF:

0.000606

Gnomad4 AMR exome

AF:

0.0000852

Gnomad4 ASJ exome

AF:

0.00201

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000351

Gnomad4 FIN exome

AF:

0.0000260

Gnomad4 NFE exome

AF:

0.00265

Gnomad4 OTH exome

AF:

0.00195

GnomAD4 genome

AF:

0.00113

AC:

127

AN:

112387

Hom.:

Cov.:

AF XY:

0.000724

AC XY:

AN XY:

34549

show subpopulations

Gnomad4 AFR

AF:

0.000452

Gnomad4 AMR

AF:

0.000281

Gnomad4 ASJ

AF:

0.00264

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00190

Gnomad4 OTH

AF:

0.00130

Alfa

AF:

0.00216

Hom.:

Bravo

AF:

0.00120

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00277

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00149

AC:

ExAC

AF:

0.000923

AC:

112

EpiCase

AF:

0.00142

EpiControl

AF:

0.00160

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.987G>A (p.M329I) alteration is located in exon 1 (coding exon 1) of the MAGEE2 gene. This alteration results from a G to A substitution at nucleotide position 987, causing the methionine (M) at amino acid position 329 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.94

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.0092

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.46

M_CAP

Benign

0.0016

MetaRNN

Benign

0.0098

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.0

REVEL

Benign

0.059

Sift

Benign

0.065

Sift4G

Benign

0.099

Polyphen

0.0020

Vest4

0.067

MutPred

0.62

Gain of catalytic residue at M329 (P = 0.0102);

MVP

0.50

MPC

0.012

ClinPred

0.0061

GERP RS

0.86

Varity_R

0.21

gMVP

0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over