X-151924132-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001011548.1(MAGEA4):​c.468C>T​(p.Ser156Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000686 in 1,210,600 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 25 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.000074 ( 0 hom. 24 hem. )

Consequence

MAGEA4
NM_001011548.1 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.04
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 -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant X-151924132-C-T is Benign according to our data. Variant chrX-151924132-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2661657.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-3.04 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 24 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAGEA4NM_001011548.1 linkc.468C>T p.Ser156Ser synonymous_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.468C>T p.Ser156Ser synonymous_variant Exon 3 of 3 2 NM_001011548.1 ENSP00000276344.2 P43358

Frequencies

GnomAD3 genomes
AF:
0.0000178
AC:
2
AN:
112358
Hom.:
0
Cov.:
23
AF XY:
0.0000290
AC XY:
1
AN XY:
34522
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000563
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:
183468
Hom.:
0
AF XY:
0.0000294
AC XY:
2
AN XY:
67914
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000365
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000216
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000244
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000738
AC:
81
AN:
1098187
Hom.:
0
Cov.:
36
AF XY:
0.0000660
AC XY:
24
AN XY:
363551
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000284
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000265
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000843
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
AF:
0.0000178
AC:
2
AN:
112413
Hom.:
0
Cov.:
23
AF XY:
0.0000289
AC XY:
1
AN XY:
34587
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000564
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Mar 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

MAGEA4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.26
DANN
Benign
0.67

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: rs202047929; hg19: chrX-151092604; COSMIC: COSV52341649; API