rs778001194

Variant summary

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

The NM_001011548.1(MAGEA4):​c.499G>A​(p.Val167Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,210,525 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V167L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000071 ( 0 hom., 4 hem., cov: 24)
Exomes 𝑓: 0.0000091 ( 0 hom. 2 hem. )

Consequence

MAGEA4
NM_001011548.1 missense

Scores

1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.338
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.04034248).
BS2
High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAGEA4NM_001011548.1 linkc.499G>A p.Val167Met 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.499G>A p.Val167Met missense_variant Exon 3 of 3 2 NM_001011548.1 ENSP00000276344.2 P43358

Frequencies

GnomAD3 genomes
AF:
0.0000712
AC:
8
AN:
112367
Hom.:
0
Cov.:
24
AF XY:
0.000116
AC XY:
4
AN XY:
34525
show subpopulations
Gnomad AFR
AF:
0.000259
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000327
AC:
6
AN:
183397
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
67853
show subpopulations
Gnomad AFR exome
AF:
0.000380
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:
0.0000122
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000911
AC:
10
AN:
1098106
Hom.:
0
Cov.:
36
AF XY:
0.00000550
AC XY:
2
AN XY:
363474
show subpopulations
Gnomad4 AFR exome
AF:
0.000303
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:
0.00000238
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000712
AC:
8
AN:
112419
Hom.:
0
Cov.:
24
AF XY:
0.000116
AC XY:
4
AN XY:
34587
show subpopulations
Gnomad4 AFR
AF:
0.000258
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000907
ExAC
AF:
0.0000247
AC:
3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
2.8
DANN
Uncertain
0.99
DEOGEN2
Benign
0.064
T;T;.;T;.;.;T;.;.;.;T;T;T;.
FATHMM_MKL
Benign
0.0082
N
LIST_S2
Benign
0.74
T;T;.;.;.;.;.;T;T;.;.;.;.;T
M_CAP
Benign
0.0029
T
MetaRNN
Benign
0.040
T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
.;L;.;L;.;.;L;.;.;.;L;L;L;.
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-2.2
N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
0.081
Sift
Benign
0.14
T;T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G
Benign
0.11
T;T;T;T;D;D;T;T;T;D;T;T;T;D
Polyphen
0.99
.;D;.;D;.;.;D;.;.;.;D;D;D;.
Vest4
0.12
MVP
0.12
MPC
0.0059
ClinPred
0.041
T
GERP RS
-0.91
Varity_R
0.16
gMVP
0.18

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: rs778001194; hg19: chrX-151092635; COSMIC: COSV52340613; API