Variant X-30218657-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000378988.5(MAGEB2):c.77A>G(p.Asn26Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000484 in 1,208,927 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 181 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00083 ( 0 hom., 20 hem., cov: 23)

Exomes 𝑓: 0.00045 ( 0 hom. 161 hem. )

Consequence

MAGEB2
ENST00000378988.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.36

Variant links:

Genes affected

MAGEB2 (HGNC:6809): (MAGE family member B2) 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. It is expressed in testis and placenta, and in a significant fraction of tumors of various histological types. The MAGEB genes are clustered on chromosome Xp22-p21. [provided by RefSeq, Jul 2008]

MAGEB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004267305).

BS2

High Hemizygotes in GnomAd4 at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEB2	NM_002364.5 linkuse as main transcript	c.77A>G	p.Asn26Ser	missense_variant	2/2	ENST00000378988.5	NP_002355.2
MAGEB2	XM_011545512.2 linkuse as main transcript	c.77A>G	p.Asn26Ser	missense_variant	2/2		XP_011543814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEB2	ENST00000378988.5 linkuse as main transcript	c.77A>G	p.Asn26Ser	missense_variant	2/2	1	NM_002364.5	ENSP00000368273	P1

Frequencies

GnomAD3 genomes

AF:

0.000828

AC:

AN:

112296

Hom.:

Cov.:

AF XY:

0.000580

AC XY:

AN XY:

34478

show subpopulations

Gnomad AFR

AF:

0.00178

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000468

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000281

Gnomad SAS

AF:

0.000374

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000564

Gnomad OTH

AF:

0.000660

GnomAD3 exomes

AF:

0.000549

AC:

AN:

178473

Hom.:

AF XY:

0.000475

AC XY:

AN XY:

63149

show subpopulations

Gnomad AFR exome

AF:

0.00226

Gnomad AMR exome

AF:

0.000295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000220

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000382

Gnomad NFE exome

AF:

0.000645

Gnomad OTH exome

AF:

0.000225

GnomAD4 exome

AF:

0.000449

AC:

492

AN:

1096572

Hom.:

Cov.:

AF XY:

0.000445

AC XY:

161

AN XY:

361974

show subpopulations

Gnomad4 AFR exome

AF:

0.00159

Gnomad4 AMR exome

AF:

0.000285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000994

Gnomad4 SAS exome

AF:

0.0000186

Gnomad4 FIN exome

AF:

0.000396

Gnomad4 NFE exome

AF:

0.000478

Gnomad4 OTH exome

AF:

0.000369

GnomAD4 genome

AF:

0.000828

AC:

AN:

112355

Hom.:

Cov.:

AF XY:

0.000579

AC XY:

AN XY:

34547

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.000468

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000281

Gnomad4 SAS

AF:

0.000375

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000564

Gnomad4 OTH

AF:

0.000652

Alfa

AF:

0.000614

Hom.:

Bravo

AF:

0.000880

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00104

AC:

ESP6500EA

AF:

0.000743

AC:

ExAC

AF:

0.000618

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2022

The c.77A>G (p.N26S) alteration is located in exon 2 (coding exon 1) of the MAGEB2 gene. This alteration results from a A to G substitution at nucleotide position 77, causing the asparagine (N) at amino acid position 26 to be replaced by a serine (S). 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

0.071

BayesDel_addAF

Benign

-0.98

BayesDel_noAF

Benign

-1.2

CADD

Benign

0.0010

DANN

Benign

0.25

DEOGEN2

Benign

0.0045

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.18

M_CAP

Benign

0.0034

MetaRNN

Benign

0.0043

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.39

REVEL

Benign

0.021

Sift

Benign

0.50

Sift4G

Benign

0.54

Polyphen

0.0

Vest4

0.045

MVP

0.17

MPC

0.0030

ClinPred

0.0065

GERP RS

-3.5

Varity_R

0.031

gMVP

0.053

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