Variant X-152766771-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_005363.5(MAGEA6):c.880A>G(p.Ser294Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,208,993 control chromosomes in the GnomAD database, including 1 homozygotes. There are 78 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 4 hem., cov: 21)

Exomes 𝑓: 0.00017 ( 1 hom. 74 hem. )

Consequence

MAGEA6
NM_005363.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.178

Variant links:

Genes affected

MAGEA6 (HGNC:6804): (MAGE family member A6) 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

MAGEA6 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=0.099959314).

BP6

Variant X-152766771-T-C is Benign according to our data. Variant chrX-152766771-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3341591.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEA6	NM_005363.5 linkuse as main transcript	c.880A>G	p.Ser294Gly	missense_variant	3/3	ENST00000329342.10	NP_005354.1	P43360
MAGEA6	NM_175868.4 linkuse as main transcript	c.880A>G	p.Ser294Gly	missense_variant	3/3		NP_787064.1	P43360

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEA6	ENST00000329342.10 linkuse as main transcript	c.880A>G	p.Ser294Gly	missense_variant	3/3	1	NM_005363.5	ENSP00000329199.5		P43360
MAGEA6	ENST00000616035.4 linkuse as main transcript	c.880A>G	p.Ser294Gly	missense_variant	3/3	5		ENSP00000480637.1		P43360

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

111688

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33876

show subpopulations

Gnomad AFR

AF:

0.0000326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000380

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00114

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000170

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000547

AC:

AN:

182943

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67405

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:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000166

AC:

182

AN:

1097254

Hom.:

Cov.:

AF XY:

0.000204

AC XY:

AN XY:

362614

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000568

Gnomad4 ASJ exome

AF:

0.000413

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000943

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000666

Gnomad4 OTH exome

AF:

0.000565

GnomAD4 genome

AF:

0.000116

AC:

AN:

111739

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33937

show subpopulations

Gnomad4 AFR

AF:

0.0000325

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000380

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000761

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000170

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000306

Hom.:

Bravo

AF:

0.000113

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

MAGEA6: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.3

DANN

Benign

0.84

DEOGEN2

Benign

0.011

T;T

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.24

.;T

M_CAP

Benign

0.00094

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.91

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.9

N;.

Sift

Benign

0.15

T;.

Sift4G

Benign

0.090

T;T

Vest4

0.091

MutPred

0.36

Loss of glycosylation at S294 (P = 0.0216);Loss of glycosylation at S294 (P = 0.0216);

MVP

0.53

ClinPred

0.040

GERP RS

-0.021

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.095

gMVP

0.25

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