Variant X-51896520-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006986.4(MAGED1):c.865G>C(p.Gly289Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000014 in 1,210,205 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 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 0.000027 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000013 ( 0 hom. 5 hem. )

Consequence

MAGED1
NM_006986.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.15

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15673617).

BS2

High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGED1	NM_006986.4 linkuse as main transcript	c.865G>C	p.Gly289Arg	missense_variant	4/13	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.865G>C	p.Gly289Arg	missense_variant	4/13	1	NM_006986.4	ENSP00000325333	P2	Q9Y5V3-1

Frequencies

GnomAD3 genomes

AF:

0.0000268

AC:

AN:

112073

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34223

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:

0.000845

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000329

AC:

AN:

182481

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

67061

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000362

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.0000127

AC:

AN:

1098083

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

363445

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000364

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.0000268

AC:

AN:

112122

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34282

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000848

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ExAC

AF:

0.0000165

AC:

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

Apr 19, 2024

The c.1033G>C (p.G345R) alteration is located in exon 5 (coding exon 4) of the MAGED1 gene. This alteration results from a G to C substitution at nucleotide position 1033, causing the glycine (G) at amino acid position 345 to be replaced by an arginine (R). 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

0.28

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

T;T;T;.

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.85

.;.;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.4

L;L;L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.3

N;N;N;N

REVEL

Benign

0.16

Sift

Benign

0.11

T;T;T;T

Sift4G

Uncertain

0.028

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.48

MutPred

0.32

Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);.;

MVP

0.60

MPC

0.092

ClinPred

0.10

GERP RS

0.44

Varity_R

0.10

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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