Variant X-76428928-C-A 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.998C>A(p.Pro333Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,094,092 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 26)

Exomes 𝑓: 0.000012 ( 0 hom. 5 hem. )

Consequence

MAGEE1
NM_020932.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -7.19

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023588717).

BS2

High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEE1	NM_020932.3 linkuse as main transcript	c.998C>A	p.Pro333Gln	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.998C>A	p.Pro333Gln	missense_variant	1/1	6	NM_020932.3	ENSP00000354912.2		Q9HCI5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000668

AC:

AN:

179606

Hom.:

AF XY:

0.0000757

AC XY:

AN XY:

66086

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000880

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:

0.0000119

AC:

AN:

1094092

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

362826

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000433

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

Cov.:

ExAC

AF:

0.0000412

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

May 11, 2022

The c.998C>A (p.P333Q) alteration is located in exon 1 (coding exon 1) of the MAGEE1 gene. This alteration results from a C to A substitution at nucleotide position 998, causing the proline (P) at amino acid position 333 to be replaced by a glutamine (Q). 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

0.083

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.098

DANN

Benign

0.62

DEOGEN2

Benign

0.0096

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.35

M_CAP

Benign

0.020

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.19

REVEL

Benign

0.019

Sift

Uncertain

0.0020

Sift4G

Benign

0.20

Polyphen

0.0040

Vest4

0.082

MutPred

0.18

Loss of catalytic residue at P333 (P = 0.0465);

MVP

0.043

MPC

0.30

ClinPred

0.064

GERP RS

-2.4

Varity_R

0.052

gMVP

0.13

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