X-149715907-C-T

Position:

chrX-149715907-C-T

Variant summary

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

The ENST00000355220.6(MAGEA11):c.421C>T(p.Leu141Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,209,754 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 0.000090 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.0000036 ( 0 hom. 1 hem. )

Consequence

MAGEA11
ENST00000355220.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.290

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=0.08127779).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAGEA11	NM_005366.5 linkuse as main transcript	c.421C>T	p.Leu141Phe	missense_variant	5/5	ENST00000355220.6	NP_005357.2
MAGEA11	NM_001011544.2 linkuse as main transcript	c.334C>T	p.Leu112Phe	missense_variant	5/5		NP_001011544.1
MAGEA11	XM_047442106.1 linkuse as main transcript	c.421C>T	p.Leu141Phe	missense_variant	8/8		XP_047298062.1
MAGEA11	XM_011531164.3 linkuse as main transcript	c.397C>T	p.Leu133Phe	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.421C>T	p.Leu141Phe	missense_variant	5/5	1	NM_005366.5	ENSP00000347358	P2	P43364-1
MAGEA11	ENST00000333104.8 linkuse as main transcript	c.334C>T	p.Leu112Phe	missense_variant	4/4	5		ENSP00000328177	A2
MAGEA11	ENST00000412632.6 linkuse as main transcript	c.334C>T	p.Leu112Phe	missense_variant	5/5	2		ENSP00000391496
MAGEA11	ENST00000518694.1 linkuse as main transcript	n.2011C>T		non_coding_transcript_exon_variant	7/7	2

Frequencies

GnomAD3 genomes

AF:

0.0000896

AC:

AN:

111562

Hom.:

Cov.:

AF XY:

0.0000593

AC XY:

AN XY:

33718

show subpopulations

Gnomad AFR

AF:

0.000326

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000546

AC:

AN:

183035

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67581

show subpopulations

Gnomad AFR exome

AF:

0.0000763

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000364

AC:

AN:

1098192

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363550

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000896

AC:

AN:

111562

Hom.:

Cov.:

AF XY:

0.0000593

AC XY:

AN XY:

33718

show subpopulations

Gnomad4 AFR

AF:

0.000326

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.00000824

AC:

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 26, 2023

The c.421C>T (p.L141F) alteration is located in exon 5 (coding exon 4) of the MAGEA11 gene. This alteration results from a C to T substitution at nucleotide position 421, causing the leucine (L) at amino acid position 141 to be replaced by a phenylalanine (F). 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

-0.58

BayesDel_noAF

Benign

-0.88

CADD

Benign

7.8

DANN

Benign

0.80

DEOGEN2

Benign

0.0064

.;T;T

FATHMM_MKL

Benign

0.0076

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.081

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.34

.;.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.85

N;N;N

REVEL

Benign

0.020

Sift

Benign

0.041

D;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.99, 0.99

.;D;D

Vest4

0.054, 0.087

MutPred

0.25

.;.;Gain of sheet (P = 0.0477);

MVP

0.10

MPC

0.67

ClinPred

0.050

GERP RS

-0.25

Varity_R

0.15

gMVP

0.044

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