X-75784694-C-A

Position:

• chrX-75784694-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_138703.5(MAGEE2):​c.358G>T​(p.Glu120Ter) 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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MAGEE2	NM_138703.5	c.358G>T	p.Glu120Ter	stop_gained	1/1	ENST00000373359.4
LOC107985664	XR_007068273.1	n.822-6598C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGEE2	ENST00000373359.4	c.358G>T	p.Glu120Ter	stop_gained	1/1		NM_138703.5	P1

Frequencies

GnomAD3 genomes AF: 0.0777 AC: 8657 AN: 111392 Hom.: 1137 Cov.: 23 AF XY: 0.0860 AC XY: 2888 AN XY: 33590

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

GnomAD3 exomes AF: 0.169 AC: 30761 AN: 181543 Hom.: 5395 AF XY: 0.158 AC XY: 10467 AN XY: 66323

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 SAS exome AF: 0.240

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

Gnomad4 AMR exome AF: 0.362

Gnomad4 ASJ exome AF: 0.0319

Gnomad4 EAS exome AF: 0.904

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.0517

Gnomad4 NFE exome AF: 0.0226

Gnomad4 OTH exome AF: 0.0876

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

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.0336

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.0479

Gnomad4 NFE AF: 0.0281

Gnomad4 OTH AF: 0.0749

Alfa AF: 0.0336 Hom.: 454

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
MutationTaster	Benign	2.0e-31	P
Vest4		0.24
GERP RS		3.0

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;