Variant X-26194150-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_173523.2(MAGEB6):c.304G>A(p.Val102Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000261 in 1,170,436 control chromosomes in the GnomAD database, including 22 homozygotes. There are 76 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 0.00016 ( 0 hom., 3 hem., cov: 20)

Exomes 𝑓: 0.00027 ( 22 hom. 73 hem. )

Consequence

MAGEB6
NM_173523.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.61

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027448982).

BP6

Variant X-26194150-G-A is Benign according to our data. Variant chrX-26194150-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2391750.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEB6	NM_173523.2 linkuse as main transcript	c.304G>A	p.Val102Ile	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.304G>A	p.Val102Ile	missense_variant	2/2	1	NM_173523.2	ENSP00000368320	P1

Frequencies

GnomAD3 genomes

AF:

0.000157

AC:

AN:

107990

Hom.:

Cov.:

AF XY:

0.0000977

AC XY:

AN XY:

30718

show subpopulations

Gnomad AFR

AF:

0.0000666

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:

0.000290

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000147

AC:

AN:

176510

Hom.:

AF XY:

0.000129

AC XY:

AN XY:

62010

show subpopulations

Gnomad AFR exome

AF:

0.0000766

Gnomad AMR exome

AF:

0.0000376

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:

0.000303

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000272

AC:

289

AN:

1062446

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

339036

show subpopulations

Gnomad4 AFR exome

AF:

0.0000384

Gnomad4 AMR exome

AF:

0.0000295

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000339

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000327

Gnomad4 OTH exome

AF:

0.000424

GnomAD4 genome

AF:

0.000157

AC:

AN:

107990

Hom.:

Cov.:

AF XY:

0.0000977

AC XY:

AN XY:

30718

show subpopulations

Gnomad4 AFR

AF:

0.0000666

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:

0.000290

Gnomad4 OTH

AF:

0.00

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000692

AC:

ExAC

AF:

0.000104

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 18, 2021

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

0.077

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-1.2

CADD

Benign

0.0050

DANN

Benign

0.55

DEOGEN2

Benign

0.0018

FATHMM_MKL

Benign

0.00036

LIST_S2

Benign

0.26

M_CAP

Benign

0.0046

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.57

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.38

REVEL

Benign

0.020

Sift

Benign

0.38

Sift4G

Benign

0.52

Polyphen

0.0

Vest4

0.0030

MVP

0.030

MPC

0.019

ClinPred

0.011

GERP RS

-3.1

Varity_R

0.026

gMVP

0.044

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