dbSNP rs781805017: MAGED1:p.His25Pro (chrX-51894655-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001005333.2(MAGED1):c.74A>C(p.His25Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000652 in 1,074,125 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., 0 hem., cov: 20)

Exomes 𝑓: 0.0000065 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

MAGED1
NM_001005333.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.266

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037259787).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGED1	NM_006986.4 link	c.45+306A>C		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.45+306A>C		intron_variant	Intron 2 of 12	1	NM_006986.4	ENSP00000325333.8		Q9Y5V3-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

96531

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

24241

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000417

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000652

AC:

AN:

1074125

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

346789

show subpopulations

Gnomad4 AFR exome

AF:

0.0000401

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000207

AC:

AN:

96535

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

24259

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000417

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.99

CADD

Benign

6.6

DANN

Benign

0.55

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.27

M_CAP

Benign

0.0059

MetaRNN

Benign

0.037

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.38

PROVEAN

Benign

1.1

REVEL

Benign

0.078

Sift

Benign

0.13

Sift4G

Benign

0.21

Polyphen

0.026

Vest4

0.22

MutPred

0.16

Gain of glycosylation at H25 (P = 0.0158);

MVP

0.068

MPC

0.12

ClinPred

0.041

GERP RS

-3.9

gMVP

0.064

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over