X-75784694-C-A

Variant names:

• chrX-75784694-C-A
• rs1343879
• NM_138703.5:c.358G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_138703.5(MAGEE2):​c.358G>T​(p.Glu120*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0732 in 1,209,139 control chromosomes in the GnomAD database, including 12,772 homozygotes. There are 31,138 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.078 (1135 hom., 2890 hem., cov: 23)
  • Exomes 𝑓: 0.073 (11637 hom. 28248 hem.)
• Consequence: MAGEE2 NM_138703.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

Genes affected

MAGEE2 (HGNC:24935): (MAGE family member E2) This gene encodes a member of the E subfamily of MAGE (melanoma antigen-encoding gene) gene family. The gene is intronless and the encoded protein has two of the MAGE domains which are characteristic of MAGE family proteins. [provided by RefSeq, Sep 2011]

LOC107985664 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEE2	NM_138703.5	c.358G>T	p.Glu120*	stop_gained	Exon 1 of 1	ENST00000373359.4	NP_619648.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGEE2	ENST00000373359.4	c.358G>T	p.Glu120*	stop_gained	Exon 1 of 1	6	NM_138703.5	ENSP00000362457.2

Frequencies

GnomAD3 genomes AF: 0.0777 AC: 8657 AN: 111392 Hom.: 1137 Cov.: 23

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.00885

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.0336

Gnomad EAS AF: 0.845

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.0479

Gnomad MID AF: 0.0126

Gnomad NFE AF: 0.0281

Gnomad OTH AF: 0.0732

GnomAD2 exomes AF: 0.169 AC: 30761 AN: 181543 AF XY: 0.158

Gnomad AFR exome AF: 0.0286

Gnomad AMR exome AF: 0.382

Gnomad ASJ exome AF: 0.0310

Gnomad EAS exome AF: 0.858

Gnomad FIN exome AF: 0.0530

Gnomad NFE exome AF: 0.0268

Gnomad OTH exome AF: 0.108

GnomAD4 exome AF: 0.0727 AC: 79791 AN: 1097690 Hom.: 11637 Cov.: 32 AF XY: 0.0778 AC XY: 28248 AN XY: 363076

Gnomad4 AFR exome AF: 0.0257 AC: 679 AN: 26398

Gnomad4 AMR exome AF: 0.362 AC: 12694 AN: 35083

Gnomad4 ASJ exome AF: 0.0319 AC: 619 AN: 19374

Gnomad4 EAS exome AF: 0.904 AC: 27271 AN: 30166

Gnomad4 SAS exome AF: 0.245 AC: 13244 AN: 54061

Gnomad4 FIN exome AF: 0.0517 AC: 2092 AN: 40482

Gnomad4 NFE exome AF: 0.0226 AC: 19042 AN: 841920

Gnomad4 Remaining exome AF: 0.0876 AC: 4035 AN: 46072

GnomAD4 genome AF: 0.0777 AC: 8658 AN: 111449 Hom.: 1135 Cov.: 23 AF XY: 0.0859 AC XY: 2890 AN XY: 33657

Gnomad4 AFR AF: 0.0276 AC: 0.0276468 AN: 0.0276468

Gnomad4 AMR AF: 0.215 AC: 0.21502 AN: 0.21502

Gnomad4 ASJ AF: 0.0336 AC: 0.0335596 AN: 0.0335596

Gnomad4 EAS AF: 0.846 AC: 0.845771 AN: 0.845771

Gnomad4 SAS AF: 0.258 AC: 0.258127 AN: 0.258127

Gnomad4 FIN AF: 0.0479 AC: 0.0479249 AN: 0.0479249

Gnomad4 NFE AF: 0.0281 AC: 0.028095 AN: 0.028095

Gnomad4 OTH AF: 0.0749 AC: 0.0749337 AN: 0.0749337

Alfa AF: 0.0471 Hom.: 1272

Bravo AF: 0.0994

TwinsUK AF: 0.0235 AC: 87

ALSPAC AF: 0.0242 AC: 70

ESP6500AA AF: 0.0289 AC: 111

ESP6500EA AF: 0.0290 AC: 195

ExAC AF: 0.156 AC: 18901

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	0.0017	T
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	35
DANN	Uncertain	1.0
FATHMM_MKL	Benign	0.49	N
Vest4		0.24
GERP RS		3.0
Mutation Taster		=41/159	disease causing

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

Other links and lift over

dbSNP: rs1343879; hg19: chrX-75004529; COSMIC: COSV64897202;