Variant X-152767058-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.593A>G(p.Lys198Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000426 in 1,209,022 control chromosomes in the GnomAD database, including 2 homozygotes. There are 157 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., 63 hem., cov: 21)

Exomes 𝑓: 0.00028 ( 2 hom. 94 hem. )

Consequence

MAGEA6
NM_005363.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.54

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:

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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=0.163475).

BP6

Variant X-152767058-T-C is Benign according to our data. Variant chrX-152767058-T-C is described in ClinVar as [Benign]. Clinvar id is 742100.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 63 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEA6	NM_005363.5 linkuse as main transcript	c.593A>G	p.Lys198Arg	missense_variant	3/3	ENST00000329342.10	NP_005354.1	P43360
MAGEA6	NM_175868.4 linkuse as main transcript	c.593A>G	p.Lys198Arg	missense_variant	3/3		NP_787064.1	P43360

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAGEA6	ENST00000329342.10 linkuse as main transcript	c.593A>G	p.Lys198Arg	missense_variant	3/3	1	NM_005363.5	ENSP00000329199.5	P43360
MAGEA6	ENST00000616035.4 linkuse as main transcript	c.593A>G	p.Lys198Arg	missense_variant	3/3	5		ENSP00000480637.1	P43360
MAGEA6	ENST00000457643.1 linkuse as main transcript	c.593A>G	p.Lys198Arg	missense_variant	4/4	3		ENSP00000401806.1	E7ETG4
MAGEA6	ENST00000412733.1 linkuse as main transcript	c.593A>G	p.Lys198Arg	missense_variant	3/3	5		ENSP00000403303.1	E7EUF2

Frequencies

GnomAD3 genomes

AF:

0.00189

AC:

211

AN:

111706

Hom.:

Cov.:

AF XY:

0.00186

AC XY:

AN XY:

33904

show subpopulations

Gnomad AFR

AF:

0.00651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000755

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:

0.00

GnomAD4 exome

AF:

0.000276

AC:

303

AN:

1097263

Hom.:

Cov.:

AF XY:

0.000259

AC XY:

AN XY:

362623

show subpopulations

Gnomad4 AFR exome

AF:

0.00906

Gnomad4 AMR exome

AF:

0.000483

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000178

Gnomad4 OTH exome

AF:

0.000608

GnomAD4 genome

AF:

0.00190

AC:

212

AN:

111759

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

AN XY:

33967

show subpopulations

Gnomad4 AFR

AF:

0.00653

Gnomad4 AMR

AF:

0.000754

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:

0.00

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.00238

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;T;.;T

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.79

.;T;T;T

M_CAP

Benign

0.00073

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.6

D;.;N;N

Sift

Benign

0.082

T;.;D;D

Sift4G

Uncertain

0.048

D;D;.;.

Vest4

0.11

MutPred

0.68

Loss of ubiquitination at K198 (P = 0.0167);Loss of ubiquitination at K198 (P = 0.0167);Loss of ubiquitination at K198 (P = 0.0167);Loss of ubiquitination at K198 (P = 0.0167);

MVP

0.45

ClinPred

0.97

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.31

gMVP

0.70

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