dbSNP rs146569098: MAGEA4:p.Glu58Gly (chrX-151923837-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 3542013.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001011548.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAGEA4	NM_001011548.1	MANE Select	c.173A>G	p.Glu58Gly	missense	Exon 3 of 3	NP_001011548.1	P43358
MAGEA4	NM_001011549.1		c.173A>G	p.Glu58Gly	missense	Exon 3 of 3	NP_001011549.1	P43358
MAGEA4	NM_001011550.1		c.173A>G	p.Glu58Gly	missense	Exon 3 of 3	NP_001011550.1	P43358

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAGEA4	ENST00000276344.6	TSL:2 MANE Select	c.173A>G	p.Glu58Gly	missense	Exon 3 of 3	ENSP00000276344.2	P43358
MAGEA4	ENST00000360243.6	TSL:1	c.173A>G	p.Glu58Gly	missense	Exon 3 of 3	ENSP00000353379.2	P43358
MAGEA4	ENST00000370335.5	TSL:1	c.173A>G	p.Glu58Gly	missense	Exon 3 of 3	ENSP00000359360.1	P43358

Frequencies

GnomAD3 genomes

AF:

0.000206

AC:

AN:

111745

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000664

AC:

AN:

180748

AF XY:

0.0000306

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 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

African (AFR)

AF:

0.000683

AC:

AN:

26370

American (AMR)

AF:

0.0000570

AC:

AN:

35066

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19278

East Asian (EAS)

AF:

0.00

AC:

AN:

30197

South Asian (SAS)

AF:

0.00

AC:

AN:

53931

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40206

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4121

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841509

Other (OTH)

AF:

0.0000217

AC:

AN:

46034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000206

AC:

AN:

111745

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

AN XY:

33909

show subpopulations

African (AFR)

AF:

0.000749

AC:

AN:

30714

American (AMR)

AF:

0.00

AC:

AN:

10638

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2648

East Asian (EAS)

AF:

0.00

AC:

AN:

3515

South Asian (SAS)

AF:

0.00

AC:

AN:

2606

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6127

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53075

Other (OTH)

AF:

0.00

AC:

AN:

1501

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000147

ESP6500AA

AF:

0.00130

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000577

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0020

(source)

DANN

Benign

0.095

DEOGEN2

Benign

0.00063

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.083

M_CAP

Benign

0.0011

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.060

PhyloP100

-3.0

PrimateAI

Benign

0.24

PROVEAN

Benign

2.7

REVEL

Benign

0.012

Sift

Benign

0.55

Sift4G

Benign

0.71

Polyphen

0.0

Vest4

0.011

MVP

0.068

MPC

0.0030

ClinPred

0.015

GERP RS

-0.61

Varity_R

0.028

gMVP

0.11

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over