Variant X-54810837-G-C 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_177433.3(MAGED2):c.554G>C(p.Gly185Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000291 in 1,169,845 control chromosomes in the GnomAD database, including 1 homozygotes. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000030 ( 1 hom. 8 hem. )

Consequence

MAGED2
NM_177433.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.26

Variant links:

Genes affected

MAGED2 (HGNC:16353): (MAGE family member D2) This gene is a member of the MAGED gene family. The MAGED genes are clustered on chromosome Xp11. This gene is located in Xp11.2, a hot spot for X-linked intellectual disability (XLID). Mutations in this gene cause a form of transient antenatal Bartter's syndrome. This gene may also be involved in several types of cancer, including breast cancer and melanoma. The protein encoded by this gene is progressively recruited from the cytoplasm to the nucleoplasm during the interphase and after nucleolar stress and is thus thought to play a role in cell cycle regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]

MAGED2 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=0.031939477).

BP6

Variant X-54810837-G-C is Benign according to our data. Variant chrX-54810837-G-C is described in ClinVar as [Benign]. Clinvar id is 2420281.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MAGED2	NM_177433.3 linkuse as main transcript	c.554G>C	p.Gly185Ala	missense_variant	4/13	ENST00000375068.6
MAGED2	NM_014599.6 linkuse as main transcript	c.554G>C	p.Gly185Ala	missense_variant	4/13
MAGED2	NM_201222.3 linkuse as main transcript	c.554G>C	p.Gly185Ala	missense_variant	4/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGED2	ENST00000375068.6 linkuse as main transcript	c.554G>C	p.Gly185Ala	missense_variant	4/13	1	NM_177433.3	P1	Q9UNF1-1

Frequencies

GnomAD3 genomes

AF:

0.0000177

AC:

AN:

112698

Hom.:

Cov.:

AF XY:

0.0000287

AC XY:

AN XY:

34852

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000187

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000199

AC:

AN:

150875

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

48083

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00142

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:

0.00

Gnomad OTH exome

AF:

0.000279

GnomAD4 exome

AF:

0.0000303

AC:

AN:

1057147

Hom.:

Cov.:

AF XY:

0.0000235

AC XY:

AN XY:

340215

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00111

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000122

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000177

AC:

AN:

112698

Hom.:

Cov.:

AF XY:

0.0000287

AC XY:

AN XY:

34852

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000187

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.000214

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 13, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

T;T;T;T;T;T;T;T

FATHMM_MKL

Uncertain

0.92

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.032

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.81

L;.;L;.;L;L;.;L

MutationTaster

Benign

0.65

N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

0.43

N;.;N;.;N;N;N;N

REVEL

Benign

0.083

Sift

Benign

0.21

T;.;T;.;T;T;T;T

Sift4G

Benign

0.75

T;T;T;T;T;T;T;T

Polyphen

0.80

P;P;P;.;P;P;P;P

Vest4

0.20

MutPred

0.15

Loss of loop (P = 0.0603);.;Loss of loop (P = 0.0603);.;Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);.;Loss of loop (P = 0.0603);

MVP

0.70

MPC

1.3

ClinPred

0.087

GERP RS

3.9

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Varity_R

0.14

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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