Genetic Variant MAGEB6B:p.Ser258Ser (chrX-26161374-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001396029.1(MAGEB6B):c.774C>T(p.Ser258Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 698,242 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 59 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., 4 hem., cov: 22)

Exomes 𝑓: 0.00018 ( 0 hom. 55 hem. )

Consequence

MAGEB6B
NM_001396029.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.96

Variant links:

Genes affected

MAGEB6B (HGNC:28824): (MAGE family member B6B) Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MAGEB6B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant X-26161374-C-T is Benign according to our data. Variant chrX-26161374-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2660203.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.96 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEB6B	NM_001396029.1 link	c.774C>T	p.Ser258Ser	synonymous_variant	Exon 1 of 1	ENST00000416929.3	NP_001382958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGEB6B	ENST00000416929.3 link	c.774C>T	p.Ser258Ser	synonymous_variant	Exon 1 of 1	6	NM_001396029.1	ENSP00000488257.1		A0A0J9YX57

Frequencies

GnomAD3 genomes

AF:

0.0000988

AC:

AN:

111282

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

33484

show subpopulations

Gnomad AFR

AF:

0.0000654

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000956

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000769

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000113

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000175

AC:

AN:

182949

Hom.:

AF XY:

0.000237

AC XY:

AN XY:

67467

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000182

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000786

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000135

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000175

AC:

103

AN:

586960

Hom.:

Cov.:

AF XY:

0.000291

AC XY:

AN XY:

189096

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000359

Gnomad4 SAS exome

AF:

0.00119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000101

Gnomad4 OTH exome

AF:

0.000103

GnomAD4 genome

AF:

0.0000988

AC:

AN:

111282

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

33484

show subpopulations

Gnomad4 AFR

AF:

0.0000654

Gnomad4 AMR

AF:

0.0000956

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000769

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000113

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.000102

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MAGEB6B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.48

DANN

Benign

0.91

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