X-149715791-G-A

Position:

chrX-149715791-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000355220.6(MAGEA11):c.305G>A(p.Arg102Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000416 in 1,201,967 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.0000037 ( 0 hom. 2 hem. )

Consequence

MAGEA11
ENST00000355220.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.961

Variant links:

Genes affected

MAGEA11 (HGNC:6798): (MAGE family member A11) 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. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MAGEA11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09636167).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAGEA11	NM_005366.5 linkuse as main transcript	c.305G>A	p.Arg102Gln	missense_variant	5/5	ENST00000355220.6	NP_005357.2
MAGEA11	NM_001011544.2 linkuse as main transcript	c.218G>A	p.Arg73Gln	missense_variant	5/5		NP_001011544.1
MAGEA11	XM_047442106.1 linkuse as main transcript	c.305G>A	p.Arg102Gln	missense_variant	8/8		XP_047298062.1
MAGEA11	XM_011531164.3 linkuse as main transcript	c.281G>A	p.Arg94Gln	missense_variant	4/4		XP_011529466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEA11	ENST00000355220.6 linkuse as main transcript	c.305G>A	p.Arg102Gln	missense_variant	5/5	1	NM_005366.5	ENSP00000347358	P2	P43364-1
MAGEA11	ENST00000333104.8 linkuse as main transcript	c.218G>A	p.Arg73Gln	missense_variant	4/4	5		ENSP00000328177	A2
MAGEA11	ENST00000412632.6 linkuse as main transcript	c.218G>A	p.Arg73Gln	missense_variant	5/5	2		ENSP00000391496
MAGEA11	ENST00000518694.1 linkuse as main transcript	n.1895G>A		non_coding_transcript_exon_variant	7/7	2

Frequencies

GnomAD3 genomes

AF:

0.00000899

AC:

AN:

111240

Hom.:

Cov.:

AF XY:

0.0000299

AC XY:

AN XY:

33468

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000951

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:

0.00

GnomAD3 exomes

AF:

0.00000578

AC:

AN:

173160

Hom.:

AF XY:

0.00

AC XY:

AN XY:

58998

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:

0.0000626

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000367

AC:

AN:

1090727

Hom.:

Cov.:

AF XY:

0.00000559

AC XY:

AN XY:

357647

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000190

Gnomad4 FIN exome

AF:

0.0000248

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.0000219

GnomAD4 genome

AF:

0.00000899

AC:

AN:

111240

Hom.:

Cov.:

AF XY:

0.0000299

AC XY:

AN XY:

33468

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000951

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:

0.00

Bravo

AF:

0.00000378

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

Nov 08, 2021

The c.305G>A (p.R102Q) alteration is located in exon 5 (coding exon 4) of the MAGEA11 gene. This alteration results from a G to A substitution at nucleotide position 305, causing the arginine (R) at amino acid position 102 to be replaced by a glutamine (Q). 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

0.094

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.44

DANN

Benign

0.81

DEOGEN2

Benign

0.0073

.;T;T

FATHMM_MKL

Benign

0.0062

LIST_S2

Benign

0.50

T;T;T

M_CAP

Benign

0.00090

MetaRNN

Benign

0.096

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

.;.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.040

N;N;N

REVEL

Benign

0.011

Sift

Benign

0.25

T;T;T

Sift4G

Benign

0.39

T;T;T

Polyphen

0.0010

.;B;B

Vest4

0.089, 0.060

MutPred

0.49

.;.;Gain of sheet (P = 0.1208);

MVP

0.24

MPC

0.29

ClinPred

0.026

GERP RS

-1.4

Varity_R

0.065

gMVP

0.061

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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