X-54810072-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_177433.3(MAGED2):c.396A>G(p.Thr132Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,203,510 control chromosomes in the GnomAD database, including 60,298 homozygotes. There are 145,279 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 8802 hom., 13642 hem., cov: 21)

Exomes 𝑓: 0.37 ( 51496 hom. 131637 hem. )

Consequence

MAGED2
NM_177433.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -4.75

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BP6

Variant X-54810072-A-G is Benign according to our data. Variant chrX-54810072-A-G is described in ClinVar as [Benign]. Clinvar id is 1258035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-54810072-A-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-4.75 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGED2	NM_177433.3 link	c.396A>G	p.Thr132Thr	synonymous_variant	Exon 3 of 13	ENST00000375068.6	NP_803182.1	Q9UNF1-1A0A024R9Y7
MAGED2	NM_014599.6 link	c.396A>G	p.Thr132Thr	synonymous_variant	Exon 3 of 13		NP_055414.2	Q9UNF1-1A0A024R9Y7
MAGED2	NM_201222.3 link	c.396A>G	p.Thr132Thr	synonymous_variant	Exon 3 of 13		NP_957516.1	Q9UNF1-1A0A024R9Y7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGED2	ENST00000375068.6 link	c.396A>G	p.Thr132Thr	synonymous_variant	Exon 3 of 13	1	NM_177433.3	ENSP00000364209.1		Q9UNF1-1

Frequencies

GnomAD3 genomes

AF:

0.446

AC:

48518

AN:

108902

Hom.:

8808

Cov.:

AF XY:

0.435

AC XY:

13592

AN XY:

31246

show subpopulations

Gnomad AFR

AF:

0.668

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.400

Gnomad ASJ

AF:

0.373

Gnomad EAS

AF:

0.618

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.398

Gnomad MID

AF:

0.270

Gnomad NFE

AF:

0.336

Gnomad OTH

AF:

0.411

GnomAD3 exomes

AF:

0.400

AC:

69792

AN:

174666

Hom.:

10295

AF XY:

0.383

AC XY:

23198

AN XY:

60506

show subpopulations

Gnomad AFR exome

AF:

0.672

Gnomad AMR exome

AF:

0.345

Gnomad ASJ exome

AF:

0.376

Gnomad EAS exome

AF:

0.629

Gnomad SAS exome

AF:

0.386

Gnomad FIN exome

AF:

0.399

Gnomad NFE exome

AF:

0.344

Gnomad OTH exome

AF:

0.344

GnomAD4 exome

AF:

0.366

AC:

400152

AN:

1094553

Hom.:

51496

Cov.:

AF XY:

0.365

AC XY:

131637

AN XY:

360431

show subpopulations

Gnomad4 AFR exome

AF:

0.679

Gnomad4 AMR exome

AF:

0.355

Gnomad4 ASJ exome

AF:

0.379

Gnomad4 EAS exome

AF:

0.637

Gnomad4 SAS exome

AF:

0.390

Gnomad4 FIN exome

AF:

0.404

Gnomad4 NFE exome

AF:

0.342

Gnomad4 OTH exome

AF:

0.377

GnomAD4 genome

AF:

0.446

AC:

48552

AN:

108957

Hom.:

8802

Cov.:

AF XY:

0.436

AC XY:

13642

AN XY:

31311

show subpopulations

Gnomad4 AFR

AF:

0.669

Gnomad4 AMR

AF:

0.399

Gnomad4 ASJ

AF:

0.373

Gnomad4 EAS

AF:

0.618

Gnomad4 SAS

AF:

0.367

Gnomad4 FIN

AF:

0.398

Gnomad4 NFE

AF:

0.336

Gnomad4 OTH

AF:

0.406

Alfa

AF:

0.362

Hom.:

16996

Bravo

AF:

0.461

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bartter disease type 5

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.5

DANN

Benign

0.67

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over