Genetic Variant MAGEA8:p.Tyr242Tyr (chrX-149884998-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

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

The NM_005364.5(MAGEA8):c.726T>C(p.Tyr242Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000539 in 1,206,859 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 29 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 0.000045 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.000055 ( 0 hom. 28 hem. )

Consequence

MAGEA8
NM_005364.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.584

Variant links:

Genes affected

MAGEA8 (HGNC:6806): (MAGE family member A8) This gene is a member of the MAGEA gene family. The members of this family encode proteins with 50 to 80% sequence identity to each other. The promoters and first exons of the MAGEA genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. The MAGEA genes are clustered at chromosomal location Xq28. They have been implicated in some hereditary disorders, such as dyskeratosis congenita. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Oct 2009]

MAGEA8 links:

MAGEA8-AS1 (HGNC:45093): (MAGEA8 antisense RNA 1)

MAGEA8-AS1 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=-1.0).

BP6

Variant X-149884998-T-C is Benign according to our data. Variant chrX-149884998-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2661622.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.584 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 28 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEA8	NM_005364.5 link	c.726T>C	p.Tyr242Tyr	synonymous_variant	Exon 3 of 3	ENST00000286482.6	NP_005355.2	P43361B2R9W4
MAGEA8	NM_001166400.2 link	c.726T>C	p.Tyr242Tyr	synonymous_variant	Exon 4 of 4		NP_001159872.1	P43361B2R9W4
MAGEA8	NM_001166401.2 link	c.726T>C	p.Tyr242Tyr	synonymous_variant	Exon 3 of 3		NP_001159873.1	P43361B2R9W4
MAGEA8-AS1	NR_102703.1 link	n.81-2500A>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAGEA8	ENST00000286482.6 link	c.726T>C	p.Tyr242Tyr	synonymous_variant	Exon 3 of 3	1	NM_005364.5	ENSP00000286482.1	P43361
MAGEA8	ENST00000535454.5 link	c.726T>C	p.Tyr242Tyr	synonymous_variant	Exon 4 of 4	3		ENSP00000438293.1	P43361
MAGEA8	ENST00000542674.5 link	c.726T>C	p.Tyr242Tyr	synonymous_variant	Exon 3 of 3	3		ENSP00000443776.1	P43361

Frequencies

GnomAD3 genomes

AF:

0.0000448

AC:

AN:

111598

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33792

show subpopulations

Gnomad AFR

AF:

0.0000325

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:

0.0000566

Gnomad OTH

AF:

0.000669

GnomAD3 exomes

AF:

0.0000112

AC:

AN:

178559

Hom.:

AF XY:

0.0000315

AC XY:

AN XY:

63415

show subpopulations

Gnomad AFR exome

AF:

0.0000761

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:

0.00

Gnomad NFE exome

AF:

0.0000125

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000548

AC:

AN:

1095261

Hom.:

Cov.:

AF XY:

0.0000776

AC XY:

AN XY:

360927

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000285

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:

0.0000654

Gnomad4 OTH exome

AF:

0.0000653

GnomAD4 genome

AF:

0.0000448

AC:

AN:

111598

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33792

show subpopulations

Gnomad4 AFR

AF:

0.0000325

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:

0.0000566

Gnomad4 OTH

AF:

0.000669

Bravo

AF:

0.0000227

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MAGEA8: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.1

DANN

Benign

0.81

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