chrX-30250756-A-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_177404.3(MAGEB1):c.263A>T(p.Glu88Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000911 in 1,097,461 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000091 ( 0 hom. 3 hem. )

Consequence

MAGEB1
NM_177404.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.707

Publications

1 publications found

Variant links:

Genes affected

MAGEB1 (HGNC:6808): (MAGE family member B1) This gene is a member of the MAGEB gene family. The members of this family have their entire coding sequences located in the last exon, and the encoded proteins show 50 to 68% sequence identity to each other. The promoters and first exons of the MAGEB genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. This gene is localized in the DSS (dosage-sensitive sex reversal) critical region, and expressed in testis and in a significant fraction of tumors of various histological types. This gene and other MAGEB members are clustered on chromosome Xp22-p21. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene, however, the full length nature of some variants has not been defined. [provided by RefSeq, Jul 2008]

MAGEB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13631424).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEB1	NM_177404.3 link	c.263A>T	p.Glu88Val	missense_variant	Exon 2 of 2	ENST00000397548.4	NP_796379.1	P43366
MAGEB1	NM_002363.5 link	c.263A>T	p.Glu88Val	missense_variant	Exon 4 of 4		NP_002354.2	P43366
MAGEB1	NM_177415.3 link	c.263A>T	p.Glu88Val	missense_variant	Exon 3 of 3		NP_803134.1	P43366

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAGEB1	ENST00000397548.4 link	c.263A>T	p.Glu88Val	missense_variant	Exon 2 of 2	1	NM_177404.3	ENSP00000380681.2	P43366
MAGEB1	ENST00000378981.8 link	c.263A>T	p.Glu88Val	missense_variant	Exon 4 of 4	1		ENSP00000368264.3	P43366
MAGEB1	ENST00000397550.6 link	c.263A>T	p.Glu88Val	missense_variant	Exon 3 of 3	1		ENSP00000380683.1	P43366

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000111

AC:

AN:

180490

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000249

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000911

AC:

AN:

1097461

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

362871

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26395

American (AMR)

AF:

0.00

AC:

AN:

35143

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19374

East Asian (EAS)

AF:

0.00

AC:

AN:

30182

South Asian (SAS)

AF:

0.0000186

AC:

AN:

53885

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40500

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.00000950

AC:

AN:

841777

Other (OTH)

AF:

0.0000217

AC:

AN:

46073

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 26, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.263A>T (p.E88V) alteration is located in exon 4 (coding exon 1) of the MAGEB1 gene. This alteration results from a A to T substitution at nucleotide position 263, causing the glutamic acid (E) at amino acid position 88 to be replaced by a valine (V). 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

0.14

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.050

T;T;T

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.19

.;T;.

M_CAP

Benign

0.0085

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

M;M;M

PhyloP100

0.71

PrimateAI

Benign

0.22

PROVEAN

Pathogenic

-5.2

D;D;D

REVEL

Benign

0.029

Sift

Uncertain

0.0090

D;D;D

Sift4G

Uncertain

0.016

D;D;D

Polyphen

0.41

B;B;B

Vest4

0.17

MutPred

0.21

Gain of catalytic residue at E88 (P = 0.0596);Gain of catalytic residue at E88 (P = 0.0596);Gain of catalytic residue at E88 (P = 0.0596);

MVP

0.34

MPC

0.10

ClinPred

0.22

GERP RS

1.5

Varity_R

0.28

gMVP

0.31

Mutation Taster

=99/1

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

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chrX-30250756-A-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over