Variant X-149716276-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000355220.6(MAGEA11):c.790T>C(p.Phe264Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000893 in 112,009 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Consequence

MAGEA11
ENST00000355220.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.178

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAGEA11	NM_005366.5 linkuse as main transcript	c.790T>C	p.Phe264Leu	missense_variant	5/5	ENST00000355220.6	NP_005357.2
MAGEA11	NM_001011544.2 linkuse as main transcript	c.703T>C	p.Phe235Leu	missense_variant	5/5		NP_001011544.1
MAGEA11	XM_047442106.1 linkuse as main transcript	c.790T>C	p.Phe264Leu	missense_variant	8/8		XP_047298062.1
MAGEA11	XM_011531164.3 linkuse as main transcript	c.766T>C	p.Phe256Leu	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.790T>C	p.Phe264Leu	missense_variant	5/5	1	NM_005366.5	ENSP00000347358	P2	P43364-1
MAGEA11	ENST00000333104.8 linkuse as main transcript	c.703T>C	p.Phe235Leu	missense_variant	4/4	5		ENSP00000328177	A2
MAGEA11	ENST00000412632.6 linkuse as main transcript	c.703T>C	p.Phe235Leu	missense_variant	5/5	2		ENSP00000391496
MAGEA11	ENST00000518694.1 linkuse as main transcript	n.2380T>C		non_coding_transcript_exon_variant	7/7	2

Frequencies

GnomAD3 genomes

AF:

0.00000893

AC:

AN:

112009

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34193

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

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000893

AC:

AN:

112009

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34193

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

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

Mar 21, 2023

The c.790T>C (p.F264L) alteration is located in exon 5 (coding exon 4) of the MAGEA11 gene. This alteration results from a T to C substitution at nucleotide position 790, causing the phenylalanine (F) at amino acid position 264 to be replaced by a leucine (L). 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

Pathogenic

0.74

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.044

.;T;T

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.67

T;T;T

M_CAP

Benign

0.0021

MetaRNN

Uncertain

0.48

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

.;.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-5.2

D;D;D

REVEL

Benign

0.14

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.32

T;T;T

Polyphen

0.91, 0.88

.;P;P

Vest4

0.26, 0.29

MutPred

0.77

.;.;Loss of catalytic residue at R265 (P = 0.3956);

MVP

0.28

MPC

0.50

ClinPred

0.40

GERP RS

-0.31

Varity_R

0.26

gMVP

0.57

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