Variant X-26194198-G-A 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.352G>A(p.Gly118Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,157,781 control chromosomes in the GnomAD database, including 2 homozygotes. There are 41 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., 16 hem., cov: 20)

Exomes 𝑓: 0.000081 ( 2 hom. 25 hem. )

Consequence

MAGEB6
NM_173523.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.135

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009853244).

BS2

High Hemizygotes in GnomAd4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEB6	NM_173523.2 linkuse as main transcript	c.352G>A	p.Gly118Ser	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.352G>A	p.Gly118Ser	missense_variant	2/2	1	NM_173523.2	ENSP00000368320	P1

Frequencies

GnomAD3 genomes

AF:

0.000607

AC:

AN:

107155

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

30527

show subpopulations

Gnomad AFR

AF:

0.00206

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000198

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:

0.000698

GnomAD3 exomes

AF:

0.000160

AC:

AN:

175483

Hom.:

AF XY:

0.000114

AC XY:

AN XY:

61203

show subpopulations

Gnomad AFR exome

AF:

0.00199

Gnomad AMR exome

AF:

0.0000755

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000809

AC:

AN:

1050577

Hom.:

Cov.:

AF XY:

0.0000762

AC XY:

AN XY:

328007

show subpopulations

Gnomad4 AFR exome

AF:

0.00266

Gnomad4 AMR exome

AF:

0.0000298

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000864

Gnomad4 OTH exome

AF:

0.000136

GnomAD4 genome

AF:

0.000606

AC:

AN:

107204

Hom.:

Cov.:

AF XY:

0.000523

AC XY:

AN XY:

30584

show subpopulations

Gnomad4 AFR

AF:

0.00206

Gnomad4 AMR

AF:

0.000198

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000690

Alfa

AF:

0.000119

Hom.:

Bravo

AF:

0.000786

ESP6500AA

AF:

0.00210

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000129

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

Apr 23, 2024

The c.352G>A (p.G118S) alteration is located in exon 2 (coding exon 1) of the MAGEB6 gene. This alteration results from a G to A substitution at nucleotide position 352, causing the glycine (G) at amino acid position 118 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

0.077

BayesDel_addAF

Benign

-0.90

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.67

DANN

Benign

0.83

DEOGEN2

Benign

0.0039

FATHMM_MKL

Benign

0.0055

LIST_S2

Benign

0.45

M_CAP

Benign

0.011

MetaRNN

Benign

0.0099

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.4

REVEL

Benign

0.048

Sift

Benign

0.20

Sift4G

Benign

0.20

Polyphen

0.59

Vest4

0.053

MVP

0.061

MPC

0.17

ClinPred

0.012

GERP RS

0.38

Varity_R

0.063

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