chrX-149713176-G-A

Position:

chrX-149713176-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000355220.6(MAGEA11):c.17G>A(p.Arg6His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000681 in 1,204,918 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 23 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000081 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000067 ( 0 hom. 22 hem. )

Consequence

MAGEA11
ENST00000355220.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.23

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022551537).

BP6

Variant X-149713176-G-A is Benign according to our data. Variant chrX-149713176-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2376120.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 22 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAGEA11	NM_005366.5 linkuse as main transcript	c.17G>A	p.Arg6His	missense_variant	2/5	ENST00000355220.6	NP_005357.2
MAGEA11	XM_047442106.1 linkuse as main transcript	c.17G>A	p.Arg6His	missense_variant	5/8		XP_047298062.1
MAGEA11	NM_001011544.2 linkuse as main transcript	c.10-1305G>A		intron_variant			NP_001011544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEA11	ENST00000355220.6 linkuse as main transcript	c.17G>A	p.Arg6His	missense_variant	2/5	1	NM_005366.5	ENSP00000347358	P2	P43364-1
MAGEA11	ENST00000333104.8 linkuse as main transcript	c.10-1305G>A		intron_variant		5		ENSP00000328177	A2
MAGEA11	ENST00000412632.6 linkuse as main transcript	c.10-1305G>A		intron_variant		2		ENSP00000391496
MAGEA11	ENST00000518694.1 linkuse as main transcript	n.382G>A		non_coding_transcript_exon_variant	5/7	2

Frequencies

GnomAD3 genomes

AF:

0.0000808

AC:

AN:

111374

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33560

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000945

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000383

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000191

AC:

AN:

178001

Hom.:

AF XY:

0.000143

AC XY:

AN XY:

62913

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000605

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000752

Gnomad SAS exome

AF:

0.0000550

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000873

Gnomad OTH exome

AF:

0.00207

GnomAD4 exome

AF:

0.0000668

AC:

AN:

1093544

Hom.:

Cov.:

AF XY:

0.0000612

AC XY:

AN XY:

359390

show subpopulations

Gnomad4 AFR exome

AF:

0.0000381

Gnomad4 AMR exome

AF:

0.000603

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000333

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000524

Gnomad4 OTH exome

AF:

0.000109

GnomAD4 genome

AF:

0.0000808

AC:

AN:

111374

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33560

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000945

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000383

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000162

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.000181

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 28, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.043

DANN

Benign

0.34

DEOGEN2

Benign

0.0024

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.54

M_CAP

Benign

0.0024

MetaRNN

Benign

0.023

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.040

REVEL

Benign

0.091

Sift

Uncertain

0.013

Sift4G

Benign

0.56

Polyphen

0.99

Vest4

0.052

MutPred

0.20

Loss of MoRF binding (P = 0.0014);

MVP

0.13

MPC

0.31

ClinPred

0.021

GERP RS

-1.7

Varity_R

0.060

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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