Genetic Variant MAGED1:p.Pro69Gln (chrX-51894787-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001005333.2(MAGED1):c.206C>A(p.Pro69Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000969 in 1,031,651 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P69L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 20)

Exomes 𝑓: 9.7e-7 ( 0 hom. 1 hem. )

Consequence

MAGED1
NM_001005333.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.534

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06078756).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005333.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAGED1	NM_006986.4	MANE Select	c.46-266C>A		intron	N/A	NP_008917.3
MAGED1	NM_001005333.2		c.206C>A	p.Pro69Gln	missense	Exon 3 of 14	NP_001005333.1	Q9Y5V3-2
MAGED1	NM_001005332.2		c.46-266C>A		intron	N/A	NP_001005332.1	Q9Y5V3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAGED1	ENST00000375695.2	TSL:1	c.206C>A	p.Pro69Gln	missense	Exon 3 of 14	ENSP00000364847.2	Q9Y5V3-2
MAGED1	ENST00000326587.12	TSL:1 MANE Select	c.46-266C>A		intron	N/A	ENSP00000325333.8	Q9Y5V3-1
MAGED1	ENST00000898271.1		c.206C>A	p.Pro69Gln	missense	Exon 3 of 14	ENSP00000568330.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.69e-7

AC:

AN:

1031651

Hom.:

Cov.:

AF XY:

0.00000301

AC XY:

AN XY:

332723

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23657

American (AMR)

AF:

0.00

AC:

AN:

21670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14865

East Asian (EAS)

AF:

0.00

AC:

AN:

29431

South Asian (SAS)

AF:

0.00

AC:

AN:

43512

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37941

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3744

European-Non Finnish (NFE)

AF:

0.00000123

AC:

AN:

813723

Other (OTH)

AF:

0.00

AC:

AN:

43108

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-1.1

CADD

Benign

1.5

(source)

DANN

Benign

0.60

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.33

M_CAP

Benign

0.018

MetaRNN

Benign

0.061

MetaSVM

Benign

-1.1

PhyloP100

-0.53

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.12

REVEL

Benign

0.046

Sift

Benign

0.28

Sift4G

Uncertain

0.025

Polyphen

0.10

Vest4

0.15

MutPred

0.14

Loss of glycosylation at P69 (P = 0.0207)

MVP

0.082

MPC

0.072

ClinPred

0.068

GERP RS

-1.9

gMVP

0.14

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over