X-151923837-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001011548.1(MAGEA4):c.173A>G(p.Glu58Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000364 in 1,208,457 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., 6 hem., cov: 24)

Exomes 𝑓: 0.000019 ( 0 hom. 5 hem. )

Consequence

MAGEA4
NM_001011548.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.05

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]

MAGEA4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0152134895).

BP6

Variant X-151923837-A-G is Benign according to our data. Variant chrX-151923837-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3542013.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEA4	NM_001011548.1 link	c.173A>G	p.Glu58Gly	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
MAGEA4	ENST00000276344.6 link	c.173A>G	p.Glu58Gly	missense_variant	Exon 3 of 3	2	NM_001011548.1	ENSP00000276344.2		P43358

Frequencies

GnomAD3 genomes

AF:

0.000206

AC:

AN:

111745

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

AN XY:

33909

show subpopulations

Gnomad AFR

AF:

0.000749

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:

0.0000664

AC:

AN:

180748

Hom.:

AF XY:

0.0000306

AC XY:

AN XY:

65462

show subpopulations

Gnomad AFR exome

AF:

0.000838

Gnomad AMR exome

AF:

0.0000369

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:

0.00

GnomAD4 exome

AF:

0.0000191

AC:

AN:

1096712

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

362308

show subpopulations

Gnomad4 AFR exome

AF:

0.000683

Gnomad4 AMR exome

AF:

0.0000570

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:

0.0000217

GnomAD4 genome

AF:

0.000206

AC:

AN:

111745

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

AN XY:

33909

show subpopulations

Gnomad4 AFR

AF:

0.000749

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:

0.000147

ESP6500AA

AF:

0.00130

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Sep 03, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0020

DANN

Benign

0.095

DEOGEN2

Benign

0.00063

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

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.083

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

M_CAP

Benign

0.0011

MetaRNN

Benign

0.015

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

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.060

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

PrimateAI

Benign

0.24

PROVEAN

Benign

2.7

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

REVEL

Benign

0.012

Sift

Benign

0.55

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

Sift4G

Benign

0.71

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

Polyphen

0.0

.;B;.;B;.;.;B;.;.;.;B;B;B;.

Vest4

0.011, 0.013

MVP

0.068

MPC

0.0030

ClinPred

0.015

GERP RS

-0.61

Varity_R

0.028

gMVP

0.11

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