chrX-54810014-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

Bartter disease type 5
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
antenatal Bartter syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MAGED2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 1972064.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 6 XL,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177433.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAGED2	NM_177433.3	MANE Select	c.338C>T	p.Pro113Leu	missense	Exon 3 of 13	NP_803182.1	Q9UNF1-1
MAGED2	NM_014599.6		c.338C>T	p.Pro113Leu	missense	Exon 3 of 13	NP_055414.2
MAGED2	NM_201222.3		c.338C>T	p.Pro113Leu	missense	Exon 3 of 13	NP_957516.1	Q9UNF1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAGED2	ENST00000375068.6	TSL:1 MANE Select	c.338C>T	p.Pro113Leu	missense	Exon 3 of 13	ENSP00000364209.1	Q9UNF1-1
MAGED2	ENST00000375053.6	TSL:1	c.338C>T	p.Pro113Leu	missense	Exon 3 of 12	ENSP00000364193.2	Q9UNF1-1
MAGED2	ENST00000375058.5	TSL:1	c.338C>T	p.Pro113Leu	missense	Exon 3 of 13	ENSP00000364198.1	Q9UNF1-1

Frequencies

GnomAD3 genomes

AF:

0.00000904

AC:

AN:

110664

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000467

AC:

AN:

171297

AF XY:

0.0000347

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 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

African (AFR)

AF:

0.00

AC:

AN:

26366

American (AMR)

AF:

0.000173

AC:

AN:

34761

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19254

East Asian (EAS)

AF:

0.00

AC:

AN:

30116

South Asian (SAS)

AF:

0.0000750

AC:

AN:

53325

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40102

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4131

European-Non Finnish (NFE)

AF:

0.0000143

AC:

AN:

839504

Other (OTH)

AF:

0.00

AC:

AN:

45943

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000904

AC:

AN:

110664

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32858

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30337

American (AMR)

AF:

0.00

AC:

AN:

10507

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2629

East Asian (EAS)

AF:

0.00

AC:

AN:

3527

South Asian (SAS)

AF:

0.000401

AC:

AN:

2495

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5984

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52780

Other (OTH)

AF:

0.00

AC:

AN:

1494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.94

CADD

Benign

9.0

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.024

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.76

M_CAP

Benign

0.0073

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.20

PhyloP100

0.38

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.53

REVEL

Benign

0.0080

Sift

Benign

1.0

Sift4G

Benign

0.31

Polyphen

0.014

Vest4

0.066

MutPred

0.27

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

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over