Genetic Variant NM_020932.3:c.530C>G (chrX-76428460-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_020932.3(MAGEE1):c.530C>G(p.Pro177Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000415 in 1,204,363 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000037 ( 0 hom., 1 hem., cov: 26)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

MAGEE1
NM_020932.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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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=0.048526198).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEE1	NM_020932.3 link	c.530C>G	p.Pro177Arg	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
MAGEE1	ENST00000361470.4 link	c.530C>G	p.Pro177Arg	missense_variant	Exon 1 of 1	6	NM_020932.3	ENSP00000354912.2		Q9HCI5

Frequencies

GnomAD3 genomes

AF:

0.0000374

AC:

AN:

107061

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

31609

show subpopulations

Gnomad AFR

AF:

0.000137

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

GnomAD3 exomes

AF:

0.0000111

AC:

AN:

180122

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

66038

show subpopulations

Gnomad AFR exome

AF:

0.000155

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:

9.11e-7

AC:

AN:

1097302

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363086

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

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:

0.00

GnomAD4 genome

AF:

0.0000374

AC:

AN:

107061

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

31609

show subpopulations

Gnomad4 AFR

AF:

0.000137

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

Bravo

AF:

0.0000302

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-1.1

CADD

Benign

2.1

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0066

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.36

M_CAP

Benign

0.0072

MetaRNN

Benign

0.049

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.58

REVEL

Benign

0.0040

Sift

Benign

0.094

Sift4G

Benign

0.48

Polyphen

0.39

Vest4

0.050

MutPred

0.23

Loss of glycosylation at T174 (P = 0.0339);

MVP

0.043

MPC

0.34

ClinPred

0.062

GERP RS

-1.7

Varity_R

0.053

gMVP

0.19

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over