chrX-76428424-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020932.3(MAGEE1):​c.494C>T​(p.Pro165Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,431 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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 0.0 ( 0 hom., 0 hem., cov: 26)
Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control

Consequence

MAGEE1
NM_020932.3 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.87
Variant links:
Genes affected
MAGEE1 (HGNC:24934): (MAGE family member E1) This gene encodes an alpha-dystrobrevin-associated MAGE (melanoma-associated antigen) protein, which is a member of the MAGE family. The protein contains a nuclear localization signal in the N-terminus, 30 12-amino acid repeats beginning at nt 60 with the consensus sequence ASEGPSTSVLPT, and two MAGE domains in the C-terminus. It may play a signaling role in brain, muscle, and peripheral nerve. This gene is located on X chromosome in a region containing loci linked to cognitive disability. [provided by RefSeq, Mar 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.052252173).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAGEE1NM_020932.3 linkc.494C>T p.Pro165Leu missense_variant Exon 1 of 1 ENST00000361470.4 NP_065983.1 Q9HCI5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAGEE1ENST00000361470.4 linkc.494C>T p.Pro165Leu missense_variant Exon 1 of 1 6 NM_020932.3 ENSP00000354912.2 Q9HCI5

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
110217
Hom.:
0
Cov.:
26
AF XY:
0.00
AC XY:
0
AN XY:
33299
FAILED QC
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
9.11e-7
AC:
1
AN:
1097431
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
363287
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:
0.00000119
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
110277
Hom.:
0
Cov.:
26
AF XY:
0.00
AC XY:
0
AN XY:
33363
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:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.494C>T (p.P165L) alteration is located in exon 1 (coding exon 1) of the MAGEE1 gene. This alteration results from a C to T substitution at nucleotide position 494, causing the proline (P) at amino acid position 165 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
Benign
0.070
BayesDel_addAF
Benign
-0.61
T
BayesDel_noAF
Benign
-1.1
CADD
Benign
6.1
DANN
Benign
0.95
DEOGEN2
Benign
0.0065
T
FATHMM_MKL
Benign
0.0037
N
LIST_S2
Benign
0.44
T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.052
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
1.2
L
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-0.51
N
REVEL
Benign
0.013
Sift
Benign
0.19
T
Sift4G
Benign
0.26
T
Polyphen
0.0
B
Vest4
0.022
MVP
0.043
MPC
0.33
ClinPred
0.058
T
GERP RS
-3.7
Varity_R
0.025
gMVP
0.16

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.

Other links and lift over

dbSNP: rs1423253171; hg19: chrX-75648817; COSMIC: COSV105923254; API