X-149716340-C-G

Position:

chrX-149716340-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The ENST00000355220.6(MAGEA11):c.854C>G(p.Thr285Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000536 in 111,852 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000089 ( 0 hom. 29 hem. )

Failed GnomAD Quality Control

Consequence

MAGEA11
ENST00000355220.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.86

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=0.03401947).

BP6

Variant X-149716340-C-G is Benign according to our data. Variant chrX-149716340-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2661621.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAGEA11	NM_005366.5 linkuse as main transcript	c.854C>G	p.Thr285Ser	missense_variant	5/5	ENST00000355220.6	NP_005357.2
MAGEA11	NM_001011544.2 linkuse as main transcript	c.767C>G	p.Thr256Ser	missense_variant	5/5		NP_001011544.1
MAGEA11	XM_047442106.1 linkuse as main transcript	c.854C>G	p.Thr285Ser	missense_variant	8/8		XP_047298062.1
MAGEA11	XM_011531164.3 linkuse as main transcript	c.830C>G	p.Thr277Ser	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.854C>G	p.Thr285Ser	missense_variant	5/5	1	NM_005366.5	ENSP00000347358	P2	P43364-1
MAGEA11	ENST00000333104.8 linkuse as main transcript	c.767C>G	p.Thr256Ser	missense_variant	4/4	5		ENSP00000328177	A2
MAGEA11	ENST00000412632.6 linkuse as main transcript	c.767C>G	p.Thr256Ser	missense_variant	5/5	2		ENSP00000391496
MAGEA11	ENST00000518694.1 linkuse as main transcript	n.2444C>G		non_coding_transcript_exon_variant	7/7	2

Frequencies

GnomAD3 genomes

AF:

0.0000537

AC:

AN:

111801

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

33975

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:

0.000379

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000940

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000658

AC:

AN:

182485

Hom.:

AF XY:

0.0000591

AC XY:

AN XY:

67639

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:

0.000105

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000893

AC:

AN:

1097327

Hom.:

Cov.:

AF XY:

0.0000799

AC XY:

AN XY:

363007

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:

0.000222

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000986

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.0000536

AC:

AN:

111852

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

34036

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:

0.000380

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000940

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000218

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

Jan 01, 2023

MAGEA11: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.027

DANN

Benign

0.26

DEOGEN2

Benign

0.0083

.;T;T

FATHMM_MKL

Benign

0.0075

LIST_S2

Benign

0.015

T;T;T

MetaRNN

Benign

0.034

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.62

.;.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.0030

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.33

T;T;T

Polyphen

0.021, 0.0090

.;B;B

Vest4

0.027, 0.042

MutPred

0.29

.;.;Gain of disorder (P = 0.0321);

MVP

0.28

MPC

0.23

ClinPred

0.027

GERP RS

-1.3

Varity_R

0.12

gMVP

0.24

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