Variant X-76428901-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.971C>T(p.Pro324Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000703 in 1,209,291 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 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 0.00039 ( 0 hom., 12 hem., cov: 26)

Exomes 𝑓: 0.000037 ( 0 hom. 9 hem. )

Consequence

MAGEE1
NM_020932.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.197

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=0.0053296685).

BS2

High Hemizygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEE1	NM_020932.3 linkuse as main transcript	c.971C>T	p.Pro324Leu	missense_variant	1/1	ENST00000361470.4	NP_065983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEE1	ENST00000361470.4 linkuse as main transcript	c.971C>T	p.Pro324Leu	missense_variant	1/1		NM_020932.3	ENSP00000354912	P1

Frequencies

GnomAD3 genomes

AF:

0.000391

AC:

AN:

112632

Hom.:

Cov.:

AF XY:

0.000344

AC XY:

AN XY:

34884

show subpopulations

Gnomad AFR

AF:

0.00132

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000184

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:

0.000651

GnomAD3 exomes

AF:

0.000117

AC:

AN:

179091

Hom.:

AF XY:

0.0000761

AC XY:

AN XY:

65671

show subpopulations

Gnomad AFR exome

AF:

0.00167

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:

0.0000374

AC:

AN:

1096613

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

363041

show subpopulations

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.0000285

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:

0.0000652

GnomAD4 genome

AF:

0.000390

AC:

AN:

112678

Hom.:

Cov.:

AF XY:

0.000343

AC XY:

AN XY:

34940

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.000184

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:

0.000643

ESP6500AA

AF:

0.00209

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000140

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

Apr 23, 2024

The c.971C>T (p.P324L) 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 971, causing the proline (P) at amino acid position 324 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

0.080

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-1.0

CADD

Benign

7.7

DANN

Benign

0.92

DEOGEN2

Benign

0.010

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.54

M_CAP

Benign

0.020

MetaRNN

Benign

0.0053

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.16

REVEL

Benign

0.020

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.045

Polyphen

0.0020

Vest4

0.082

MVP

0.043

MPC

0.32

ClinPred

0.021

GERP RS

-1.4

Varity_R

0.042

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