Variant X-54810020-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_177433.3(MAGED2):c.344C>T(p.Ala115Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000457 in 1,094,640 control chromosomes in the GnomAD database, including 1 homozygotes. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000046 ( 1 hom. 1 hem. )

Consequence

MAGED2
NM_177433.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.763

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11995131).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAGED2	NM_177433.3 linkuse as main transcript	c.344C>T	p.Ala115Val	missense_variant	3/13	ENST00000375068.6	NP_803182.1
MAGED2	NM_014599.6 linkuse as main transcript	c.344C>T	p.Ala115Val	missense_variant	3/13		NP_055414.2
MAGED2	NM_201222.3 linkuse as main transcript	c.344C>T	p.Ala115Val	missense_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.344C>T	p.Ala115Val	missense_variant	3/13	1	NM_177433.3	ENSP00000364209	P1	Q9UNF1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000578

AC:

AN:

173089

Hom.:

AF XY:

0.00

AC XY:

AN XY:

59009

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000230

GnomAD4 exome

AF:

0.00000457

AC:

AN:

1094640

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

360520

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.000109

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2022

The c.344C>T (p.A115V) alteration is located in exon 3 (coding exon 2) of the MAGED2 gene. This alteration results from a C to T substitution at nucleotide position 344, causing the alanine (A) at amino acid position 115 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.87

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.041

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

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.72

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

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.12

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

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.97

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

MutationTaster

Benign

0.95

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

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.6

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

REVEL

Benign

0.012

Sift

Benign

0.047

D;.;D;.;D;D;D;D

Sift4G

Benign

0.14

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

Polyphen

0.50

P;B;P;.;P;P;B;P

Vest4

0.051

MutPred

0.19

Gain of sheet (P = 0.0221);.;Gain of sheet (P = 0.0221);.;Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);.;Gain of sheet (P = 0.0221);

MVP

0.39

MPC

0.79

ClinPred

0.18

GERP RS

2.6

Varity_R

0.095

gMVP

0.063

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