Variant X-76428460-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_020932.3(MAGEE1):c.530C>T(p.Pro177Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000216 in 1,204,324 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 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 0.00015 ( 0 hom., 4 hem., cov: 26)

Exomes 𝑓: 0.0000091 ( 0 hom. 5 hem. )

Consequence

MAGEE1
NM_020932.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.91

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]

MAGEE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015553683).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEE1	NM_020932.3 linkuse as main transcript	c.530C>T	p.Pro177Leu	missense_variant	1/1	ENST00000361470.4	NP_065983.1	Q9HCI5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEE1	ENST00000361470.4 linkuse as main transcript	c.530C>T	p.Pro177Leu	missense_variant	1/1	6	NM_020932.3	ENSP00000354912.2		Q9HCI5

Frequencies

GnomAD3 genomes

AF:

0.000150

AC:

AN:

106994

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

31590

show subpopulations

Gnomad AFR

AF:

0.000514

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000967

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:

0.0000389

AC:

AN:

180122

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

66038

show subpopulations

Gnomad AFR exome

AF:

0.000543

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:

0.00000911

AC:

AN:

1097302

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

363086

show subpopulations

Gnomad4 AFR exome

AF:

0.000341

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:

0.0000217

GnomAD4 genome

AF:

0.000150

AC:

AN:

107022

Hom.:

Cov.:

AF XY:

0.000126

AC XY:

AN XY:

31640

show subpopulations

Gnomad4 AFR

AF:

0.000513

Gnomad4 AMR

AF:

0.0000967

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

ESP6500AA

AF:

0.00104

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

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

Jan 04, 2024

The c.530C>T (p.P177L) 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 530, causing the proline (P) at amino acid position 177 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

0.077

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-1.1

CADD

Benign

1.3

DANN

Benign

0.91

DEOGEN2

Benign

0.0056

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.41

M_CAP

Benign

0.0071

MetaRNN

Benign

0.016

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.48

MutationTaster

Benign

1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.65

REVEL

Benign

0.011

Sift

Benign

0.71

Sift4G

Benign

0.22

Polyphen

0.0020

Vest4

0.033

MVP

0.043

MPC

0.32

ClinPred

0.021

GERP RS

-1.7

Varity_R

0.022

gMVP

0.15

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