X-54810014-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_177433.3(MAGED2):c.338C>T(p.Pro113Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000191 in 1,204,166 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000020 ( 0 hom. 6 hem. )

Consequence

MAGED2
NM_177433.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.380

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=0.013940424).

BP6

Variant X-54810014-C-T is Benign according to our data. Variant chrX-54810014-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1972064.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MAGED2	NM_177433.3 linkuse as main transcript	c.338C>T	p.Pro113Leu	missense_variant	3/13	ENST00000375068.6
MAGED2	NM_014599.6 linkuse as main transcript	c.338C>T	p.Pro113Leu	missense_variant	3/13
MAGED2	NM_201222.3 linkuse as main transcript	c.338C>T	p.Pro113Leu	missense_variant	3/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGED2	ENST00000375068.6 linkuse as main transcript	c.338C>T	p.Pro113Leu	missense_variant	3/13	1	NM_177433.3	P1	Q9UNF1-1

Frequencies

GnomAD3 genomes

AF:

0.00000904

AC:

AN:

110664

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32858

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:

0.00

Gnomad SAS

AF:

0.000401

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000467

AC:

AN:

171297

Hom.:

AF XY:

0.0000347

AC XY:

AN XY:

57555

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000189

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000171

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000201

AC:

AN:

1093502

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

359568

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000173

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000750

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000143

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000904

AC:

AN:

110664

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32858

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:

0.000401

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.94

Cadd

Benign

9.0

Dann

Benign

0.60

DEOGEN2

Benign

0.024

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

FATHMM_MKL

Benign

0.052

M_CAP

Benign

0.0073

MetaRNN

Benign

0.014

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.20

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

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.53

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

REVEL

Benign

0.0080

Sift

Benign

1.0

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

Sift4G

Benign

0.31

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

Polyphen

0.014

B;B;B;.;B;B;B;B

Vest4

0.066

MutPred

0.27

Loss of loop (P = 0.0288);.;Loss of loop (P = 0.0288);.;Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);.;Loss of loop (P = 0.0288);

MVP

0.17

MPC

0.62

ClinPred

0.0066

GERP RS

-2.2

Varity_R

0.038

gMVP

0.073

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