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GeneBe

X-54809806-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_177433.3(MAGED2):ā€‹c.130A>Gā€‹(p.Lys44Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00455 in 1,200,730 control chromosomes in the GnomAD database, including 11 homozygotes. There are 1,745 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0027 ( 1 hom., 74 hem., cov: 22)
Exomes š‘“: 0.0047 ( 10 hom. 1671 hem. )

Consequence

MAGED2
NM_177433.3 missense

Scores

2
14

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.21
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0052116513).
BP6
Variant X-54809806-A-G is Benign according to our data. Variant chrX-54809806-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 445992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-54809806-A-G is described in Lovd as [Likely_benign].
BS2
High Hemizygotes in GnomAd4 at 74 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MAGED2NM_177433.3 linkuse as main transcriptc.130A>G p.Lys44Glu missense_variant 3/13 ENST00000375068.6
MAGED2NM_014599.6 linkuse as main transcriptc.130A>G p.Lys44Glu missense_variant 3/13
MAGED2NM_201222.3 linkuse as main transcriptc.130A>G p.Lys44Glu missense_variant 3/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MAGED2ENST00000375068.6 linkuse as main transcriptc.130A>G p.Lys44Glu missense_variant 3/131 NM_177433.3 P1Q9UNF1-1

Frequencies

GnomAD3 genomes
AF:
0.00272
AC:
301
AN:
110849
Hom.:
1
Cov.:
22
AF XY:
0.00224
AC XY:
74
AN XY:
33061
show subpopulations
Gnomad AFR
AF:
0.000791
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000857
Gnomad ASJ
AF:
0.00151
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000787
Gnomad FIN
AF:
0.00101
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00478
Gnomad OTH
AF:
0.00200
GnomAD3 exomes
AF:
0.00317
AC:
520
AN:
163982
Hom.:
1
AF XY:
0.00340
AC XY:
177
AN XY:
52068
show subpopulations
Gnomad AFR exome
AF:
0.000682
Gnomad AMR exome
AF:
0.000777
Gnomad ASJ exome
AF:
0.00209
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00190
Gnomad FIN exome
AF:
0.000820
Gnomad NFE exome
AF:
0.00591
Gnomad OTH exome
AF:
0.00312
GnomAD4 exome
AF:
0.00474
AC:
5166
AN:
1089826
Hom.:
10
Cov.:
31
AF XY:
0.00469
AC XY:
1671
AN XY:
356358
show subpopulations
Gnomad4 AFR exome
AF:
0.000647
Gnomad4 AMR exome
AF:
0.000731
Gnomad4 ASJ exome
AF:
0.00208
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00180
Gnomad4 FIN exome
AF:
0.00110
Gnomad4 NFE exome
AF:
0.00571
Gnomad4 OTH exome
AF:
0.00352
GnomAD4 genome
AF:
0.00271
AC:
301
AN:
110904
Hom.:
1
Cov.:
22
AF XY:
0.00223
AC XY:
74
AN XY:
33126
show subpopulations
Gnomad4 AFR
AF:
0.000789
Gnomad4 AMR
AF:
0.000856
Gnomad4 ASJ
AF:
0.00151
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000788
Gnomad4 FIN
AF:
0.00101
Gnomad4 NFE
AF:
0.00478
Gnomad4 OTH
AF:
0.00197
Alfa
AF:
0.00434
Hom.:
183
Bravo
AF:
0.00263
TwinsUK
AF:
0.00512
AC:
19
ALSPAC
AF:
0.00554
AC:
16
ESP6500AA
AF:
0.00156
AC:
6
ESP6500EA
AF:
0.00505
AC:
34
ExAC
AF:
0.00306
AC:
370

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingCenter for Pediatric Genomic Medicine, Children's Mercy Hospital and ClinicsAug 16, 2017- -
Benign, criteria provided, single submitterclinical testingInvitaeNov 13, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.019
T;T;T;T;T;T;T;T
FATHMM_MKL
Benign
0.54
D
M_CAP
Benign
0.0077
T
MetaRNN
Benign
0.0052
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.1
L;.;L;.;L;L;.;L
MutationTaster
Benign
1.0
N;N;N;N;N;N;N;N;N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.43
N;.;N;N;N;N;N;N
REVEL
Benign
0.22
Sift
Uncertain
0.0020
D;.;D;D;D;D;T;D
Sift4G
Benign
1.0
T;T;T;T;T;T;T;T
Polyphen
0.98
D;P;D;.;D;D;P;D
Vest4
0.068
MVP
0.66
MPC
0.88
ClinPred
0.027
T
GERP RS
3.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.26
gMVP
0.44

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.

Other links and lift over

dbSNP: rs11555928; hg19: chrX-54836239; API