X-149716067-A-G

Position:

chrX-149716067-A-G

Variant summary

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

The NM_005366.5(MAGEA11):c.581A>G(p.Asp194Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,210,275 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000032 ( 0 hom. 6 hem. )

Consequence

MAGEA11
NM_005366.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.958

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12129527).

BS2

High Hemizygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEA11	NM_005366.5 link	c.581A>G	p.Asp194Gly	missense_variant	5/5	ENST00000355220.6	NP_005357.2	P43364-1
MAGEA11	NM_001011544.2 link	c.494A>G	p.Asp165Gly	missense_variant	5/5		NP_001011544.1	P43364G5E962
MAGEA11	XM_047442106.1 link	c.581A>G	p.Asp194Gly	missense_variant	8/8		XP_047298062.1
MAGEA11	XM_011531164.3 link	c.557A>G	p.Asp186Gly	missense_variant	4/4		XP_011529466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAGEA11	ENST00000355220.6 link	c.581A>G	p.Asp194Gly	missense_variant	5/5	1	NM_005366.5	ENSP00000347358.5	P43364-1
MAGEA11	ENST00000333104.8 link	c.494A>G	p.Asp165Gly	missense_variant	4/4	5		ENSP00000328177.4	G5E962
MAGEA11	ENST00000412632.6 link	c.494A>G	p.Asp165Gly	missense_variant	5/5	2		ENSP00000391496.2	C9J2X2
MAGEA11	ENST00000518694.1 link	n.2171A>G		non_coding_transcript_exon_variant	7/7	2

Frequencies

GnomAD3 genomes

AF:

0.00000892

AC:

AN:

112094

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34264

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000273

AC:

AN:

183462

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

67908

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:

0.0000488

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.0000319

AC:

AN:

1098181

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

363535

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000392

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.00000892

AC:

AN:

112094

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34264

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Dec 04, 2021

The c.581A>G (p.D194G) alteration is located in exon 5 (coding exon 4) of the MAGEA11 gene. This alteration results from a A to G substitution at nucleotide position 581, causing the aspartic acid (D) at amino acid position 194 to be replaced by a glycine (G). 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

0.083

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.4

DANN

Benign

0.95

DEOGEN2

Benign

0.010

.;T;T

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.22

T;T;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

.;.;M

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.5

D;D;D

REVEL

Benign

0.030

Sift

Uncertain

0.029

D;D;T

Sift4G

Benign

0.072

T;D;D

Polyphen

0.010, 0.024

.;B;B

Vest4

0.10, 0.098

MVP

0.22

MPC

0.38

ClinPred

0.11

GERP RS

0.87

Varity_R

0.31

gMVP

0.22

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