X-151923719-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001011548.1(MAGEA4):​c.55C>G​(p.Gln19Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000274 in 1,209,280 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 110 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., 8 hem., cov: 23)
Exomes 𝑓: 0.00028 ( 0 hom. 102 hem. )

Consequence

MAGEA4
NM_001011548.1 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.330
Variant links:
Genes affected
MAGEA4 (HGNC:6802): (MAGE family member A4) This gene is a member of the MAGEA gene family. The members of this family encode proteins with 50 to 80% sequence identity to each other. The promoters and first exons of the MAGEA genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. The MAGEA genes are clustered at chromosomal location Xq28. They have been implicated in some hereditary disorders, such as dyskeratosis congenita. Several variants encoding the same protein have been found for this gene. [provided by RefSeq, Aug 2020]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.03758794).
BS2
High Hemizygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAGEA4NM_001011548.1 linkc.55C>G p.Gln19Glu missense_variant Exon 3 of 3 ENST00000276344.6 NP_001011548.1 P43358A0A024RC12

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAGEA4ENST00000276344.6 linkc.55C>G p.Gln19Glu missense_variant Exon 3 of 3 2 NM_001011548.1 ENSP00000276344.2 P43358

Frequencies

GnomAD3 genomes
AF:
0.000224
AC:
25
AN:
111602
Hom.:
0
Cov.:
23
AF XY:
0.000237
AC XY:
8
AN XY:
33804
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000943
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00426
Gnomad NFE
AF:
0.000434
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000202
AC:
37
AN:
182805
Hom.:
0
AF XY:
0.000148
AC XY:
10
AN XY:
67389
show subpopulations
Gnomad AFR exome
AF:
0.0000762
Gnomad AMR exome
AF:
0.000146
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:
0.000344
Gnomad OTH exome
AF:
0.000888
GnomAD4 exome
AF:
0.000279
AC:
306
AN:
1097626
Hom.:
0
Cov.:
37
AF XY:
0.000281
AC XY:
102
AN XY:
363202
show subpopulations
Gnomad4 AFR exome
AF:
0.0000379
Gnomad4 AMR exome
AF:
0.000199
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:
0.000343
Gnomad4 OTH exome
AF:
0.000195
GnomAD4 genome
AF:
0.000224
AC:
25
AN:
111654
Hom.:
0
Cov.:
23
AF XY:
0.000236
AC XY:
8
AN XY:
33866
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000942
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000434
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000356
Hom.:
1
Bravo
AF:
0.000204
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000346
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000446
AC:
3
ExAC
AF:
0.000198
AC:
24
EpiCase
AF:
0.000273
EpiControl
AF:
0.000296

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.55C>G (p.Q19E) alteration is located in exon 3 (coding exon 1) of the MAGEA4 gene. This alteration results from a C to G substitution at nucleotide position 55, causing the glutamine (Q) at amino acid position 19 to be replaced by a glutamic acid (E). 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
0.064
BayesDel_addAF
Benign
-0.67
T
BayesDel_noAF
Benign
-0.84
CADD
Benign
5.2
DANN
Benign
0.93
DEOGEN2
Benign
0.015
T;T;.;T;.;.;T;.;.;.;T;T;T;.
FATHMM_MKL
Benign
0.055
N
LIST_S2
Benign
0.70
T;T;.;.;.;.;.;T;T;.;.;.;.;T
M_CAP
Benign
0.0020
T
MetaRNN
Benign
0.038
T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
.;M;.;M;.;.;M;.;.;.;M;M;M;.
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-1.3
N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
0.026
Sift
Benign
0.058
T;T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G
Benign
0.081
T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.91
.;P;.;P;.;.;P;.;.;.;P;P;P;.
Vest4
0.18, 0.18, 0.18
MVP
0.093
MPC
0.0039
ClinPred
0.027
T
GERP RS
0.41
Varity_R
0.10
gMVP
0.093

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs147367105; hg19: chrX-151092191; API