Variant rs371038613 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001005333.2(MAGED1):c.206C>T(p.Pro69Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,140,816 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 50 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., 2 hem., cov: 20)

Exomes 𝑓: 0.00014 ( 0 hom. 48 hem. )

Consequence

MAGED1
NM_001005333.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.534

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.042477876).

BP6

Variant X-51894787-C-T is Benign according to our data. Variant chrX-51894787-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2321805.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGED1	NM_006986.4 link	c.46-266C>T		intron_variant	Intron 2 of 12	ENST00000326587.12	NP_008917.3	Q9Y5V3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGED1	ENST00000326587.12 link	c.46-266C>T		intron_variant	Intron 2 of 12	1	NM_006986.4	ENSP00000325333.8		Q9Y5V3-1

Frequencies

GnomAD3 genomes

AF:

0.0000916

AC:

AN:

109165

Hom.:

Cov.:

AF XY:

0.0000636

AC XY:

AN XY:

31453

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000289

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:

0.000114

Gnomad OTH

AF:

0.000682

GnomAD3 exomes

AF:

0.0000236

AC:

AN:

126862

Hom.:

AF XY:

0.00

AC XY:

AN XY:

42804

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000488

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000138

AC:

142

AN:

1031651

Hom.:

Cov.:

AF XY:

0.000144

AC XY:

AN XY:

332723

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000340

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000170

Gnomad4 OTH exome

AF:

0.0000696

GnomAD4 genome

AF:

0.0000916

AC:

AN:

109165

Hom.:

Cov.:

AF XY:

0.0000636

AC XY:

AN XY:

31453

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000289

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000114

Gnomad4 OTH

AF:

0.000682

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000254

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 01, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-1.1

CADD

Benign

1.8

DANN

Benign

0.63

FATHMM_MKL

Benign

0.0060

LIST_S2

Benign

0.41

M_CAP

Benign

0.014

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.56

REVEL

Benign

0.023

Sift

Benign

1.0

Sift4G

Uncertain

0.019

Polyphen

0.0

Vest4

0.10

MVP

0.068

MPC

0.079

ClinPred

0.036

GERP RS

-1.9

gMVP

0.10

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