Variant X-51895557-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006986.4(MAGED1):c.550T>C(p.Trp184Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,949 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

MAGED1
NM_006986.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.92

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:

MAGED1 (HGNC:):

MAGED1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGED1	NM_006986.4 linkuse as main transcript	c.550T>C	p.Trp184Arg	missense_variant	3/13	ENST00000326587.12	NP_008917.3	Q9Y5V3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGED1	ENST00000326587.12 linkuse as main transcript	c.550T>C	p.Trp184Arg	missense_variant	3/13	1	NM_006986.4	ENSP00000325333.8		Q9Y5V3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000548

AC:

AN:

182510

Hom.:

AF XY:

0.00

AC XY:

AN XY:

66974

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000722

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1097949

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363313

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

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

Feb 05, 2024

The c.718T>C (p.W240R) alteration is located in exon 4 (coding exon 3) of the MAGED1 gene. This alteration results from a T to C substitution at nucleotide position 718, causing the tryptophan (W) at amino acid position 240 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

Pathogenic

0.68

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

T;T;T;.

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.69

.;.;T;T

M_CAP

Benign

0.041

MetaRNN

Uncertain

0.61

D;D;D;D

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.4

L;L;L;.

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Benign

0.27

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Benign

0.85

T;T;T;T

Polyphen

1.0

D;D;D;D

Vest4

0.57

MutPred

0.42

Loss of catalytic residue at A183 (P = 0.0526);Loss of catalytic residue at A183 (P = 0.0526);Loss of catalytic residue at A183 (P = 0.0526);.;

MVP

0.61

MPC

0.14

ClinPred

0.35

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.46

gMVP

0.71

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