Variant X-54809901-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_177433.3(MAGED2):c.225T>C(p.Ala75=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000762 in 1,191,064 control chromosomes in the GnomAD database, including 5 homozygotes. There are 239 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 4 hom., 115 hem., cov: 22)

Exomes 𝑓: 0.00042 ( 1 hom. 124 hem. )

Consequence

MAGED2
NM_177433.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.189

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant X-54809901-T-C is Benign according to our data. Variant chrX-54809901-T-C is described in ClinVar as [Benign]. Clinvar id is 721675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.189 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAGED2	NM_177433.3 linkuse as main transcript	c.225T>C	p.Ala75=	synonymous_variant	3/13	ENST00000375068.6	NP_803182.1
MAGED2	NM_014599.6 linkuse as main transcript	c.225T>C	p.Ala75=	synonymous_variant	3/13		NP_055414.2
MAGED2	NM_201222.3 linkuse as main transcript	c.225T>C	p.Ala75=	synonymous_variant	3/13		NP_957516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGED2	ENST00000375068.6 linkuse as main transcript	c.225T>C	p.Ala75=	synonymous_variant	3/13	1	NM_177433.3	ENSP00000364209	P1	Q9UNF1-1

Frequencies

GnomAD3 genomes

AF:

0.00411

AC:

453

AN:

110165

Hom.:

Cov.:

AF XY:

0.00351

AC XY:

114

AN XY:

32449

show subpopulations

Gnomad AFR

AF:

0.0136

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000402

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000152

Gnomad OTH

AF:

0.00741

GnomAD3 exomes

AF:

0.00116

AC:

172

AN:

148526

Hom.:

AF XY:

0.000799

AC XY:

AN XY:

45056

show subpopulations

Gnomad AFR exome

AF:

0.0139

Gnomad AMR exome

AF:

0.000930

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:

0.0000639

Gnomad OTH exome

AF:

0.00103

GnomAD4 exome

AF:

0.000416

AC:

450

AN:

1080847

Hom.:

Cov.:

AF XY:

0.000353

AC XY:

124

AN XY:

351453

show subpopulations

Gnomad4 AFR exome

AF:

0.0129

Gnomad4 AMR exome

AF:

0.000865

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000384

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000372

Gnomad4 OTH exome

AF:

0.00108

GnomAD4 genome

AF:

0.00415

AC:

457

AN:

110217

Hom.:

Cov.:

AF XY:

0.00354

AC XY:

115

AN XY:

32511

show subpopulations

Gnomad4 AFR

AF:

0.0138

Gnomad4 AMR

AF:

0.00210

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000152

Gnomad4 OTH

AF:

0.00732

Alfa

AF:

0.00208

Hom.:

Bravo

AF:

0.00435

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.79

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