Variant X-26194411-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_173523.2(MAGEB6):c.565C>T(p.Arg189Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000412 in 1,210,355 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 176 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 0.00028 ( 0 hom., 10 hem., cov: 23)

Exomes 𝑓: 0.00043 ( 0 hom. 166 hem. )

Consequence

MAGEB6
NM_173523.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.18

Variant links:

Genes affected

MAGEB6 (HGNC:23796): (MAGE family member B6) 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 expressed in testis, 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]

MAGEB6 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=0.033280402).

BS2

High Hemizygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEB6	NM_173523.2 linkuse as main transcript	c.565C>T	p.Arg189Cys	missense_variant	2/2	ENST00000379034.1	NP_775794.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEB6	ENST00000379034.1 linkuse as main transcript	c.565C>T	p.Arg189Cys	missense_variant	2/2	1	NM_173523.2	ENSP00000368320	P1

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

112353

Hom.:

Cov.:

AF XY:

0.000290

AC XY:

AN XY:

34529

show subpopulations

Gnomad AFR

AF:

0.0000647

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000943

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000163

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000506

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000279

AC:

AN:

183056

Hom.:

AF XY:

0.000281

AC XY:

AN XY:

67536

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000125

Gnomad NFE exome

AF:

0.000599

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000426

AC:

468

AN:

1097951

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

166

AN XY:

363327

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.000247

Gnomad4 NFE exome

AF:

0.000519

Gnomad4 OTH exome

AF:

0.000412

GnomAD4 genome

AF:

0.000276

AC:

AN:

112404

Hom.:

Cov.:

AF XY:

0.000289

AC XY:

AN XY:

34592

show subpopulations

Gnomad4 AFR

AF:

0.0000646

Gnomad4 AMR

AF:

0.0000942

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000163

Gnomad4 NFE

AF:

0.000506

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000306

Hom.:

Bravo

AF:

0.000219

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000280

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000296

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

Oct 12, 2022

The c.565C>T (p.R189C) alteration is located in exon 2 (coding exon 1) of the MAGEB6 gene. This alteration results from a C to T substitution at nucleotide position 565, causing the arginine (R) at amino acid position 189 to be replaced by a cysteine (C). 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

-0.85

BayesDel_noAF

Benign

-1.1

CADD

Benign

1.8

DANN

Benign

0.71

DEOGEN2

Benign

0.0025

FATHMM_MKL

Benign

0.00059

LIST_S2

Benign

0.53

M_CAP

Benign

0.0049

MetaRNN

Benign

0.033

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.1

REVEL

Benign

0.055

Sift

Benign

0.066

Sift4G

Uncertain

0.030

Polyphen

0.0060

Vest4

0.066

MVP

0.030

MPC

0.035

ClinPred

0.022

GERP RS

-4.2

Varity_R

0.059

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