Variant X-51894750-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000375695.2(MAGED1):c.169G>A(p.Val57Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000739 in 1,146,554 control chromosomes in the GnomAD database, including 3 homozygotes. There are 197 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 1 hom., 79 hem., cov: 20)

Exomes 𝑓: 0.00043 ( 2 hom. 118 hem. )

Consequence

MAGED1
ENST00000375695.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.662

Variant links:

Genes affected

MAGED1 (HGNC:6813): (MAGE family member D1) This gene is a member of the melanoma antigen gene (MAGE) family. Most of the genes of this family encode tumor specific antigens that are not expressed in normal adult tissues except testis. Although the protein encoded by this gene shares strong homology with members of the MAGE family, it is expressed in almost all normal adult tissues. This gene has been demonstrated to be involved in the p75 neurotrophin receptor mediated programmed cell death pathway. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MAGED1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034484267).

BP6

Variant X-51894750-G-A is Benign according to our data. Variant chrX-51894750-G-A is described in ClinVar as [Benign]. Clinvar id is 790239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-51894750-G-A is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 79 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGED1	NM_006986.4 linkuse as main transcript	c.46-303G>A		intron_variant		ENST00000326587.12	NP_008917.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGED1	ENST00000326587.12 linkuse as main transcript	c.46-303G>A		intron_variant		1	NM_006986.4	ENSP00000325333	P2	Q9Y5V3-1

Frequencies

GnomAD3 genomes

AF:

0.00386

AC:

401

AN:

103852

Hom.:

Cov.:

AF XY:

0.00284

AC XY:

AN XY:

27840

show subpopulations

Gnomad AFR

AF:

0.0139

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00125

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:

0.0000390

Gnomad OTH

AF:

0.00216

GnomAD3 exomes

AF:

0.00171

AC:

224

AN:

131293

Hom.:

AF XY:

0.000999

AC XY:

AN XY:

43023

show subpopulations

Gnomad AFR exome

AF:

0.0170

Gnomad AMR exome

AF:

0.000644

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000102

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000158

Gnomad OTH exome

AF:

0.00101

GnomAD4 exome

AF:

0.000428

AC:

446

AN:

1042686

Hom.:

Cov.:

AF XY:

0.000351

AC XY:

118

AN XY:

336590

show subpopulations

Gnomad4 AFR exome

AF:

0.0157

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000225

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000853

Gnomad4 OTH exome

AF:

0.00105

GnomAD4 genome

AF:

0.00386

AC:

401

AN:

103868

Hom.:

Cov.:

AF XY:

0.00283

AC XY:

AN XY:

27866

show subpopulations

Gnomad4 AFR

AF:

0.0139

Gnomad4 AMR

AF:

0.00125

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000390

Gnomad4 OTH

AF:

0.00213

Alfa

AF:

0.000443

Hom.:

ESP6500AA

AF:

0.0169

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.00153

AC:

184

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.98

BayesDel_noAF

Benign

-1.2

CADD

Benign

2.4

DANN

Benign

0.86

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.35

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.21

REVEL

Benign

0.015

Sift

Benign

0.096

Sift4G

Benign

0.39

Polyphen

0.0

Vest4

0.030

MVP

0.11

MPC

0.064

ClinPred

0.00022

GERP RS

-4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.057

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