rs1482209977

Variant names:

• chrX-76428438-G-A
• rs1482209977
• NM_020932.3:c.508G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_020932.3(MAGEE1):​c.508G>A​(p.Glu170Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 1,209,709 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., 1 hem., cov: 26)
  • Exomes 𝑓: 0.0000036 (0 hom. 3 hem.)
• Consequence: MAGEE1 NM_020932.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.51
• Publications: 0 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.059284747).
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020932.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEE1	NM_020932.3	MANE Select	c.508G>A	p.Glu170Lys	missense	Exon 1 of 1	NP_065983.1	Q9HCI5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEE1	ENST00000361470.4	TSL:6 MANE Select	c.508G>A	p.Glu170Lys	missense	Exon 1 of 1	ENSP00000354912.2	Q9HCI5

Frequencies

GnomAD3 genomes AF: 0.0000357 AC: 4 AN: 112161 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000367

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000567

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000364 AC: 4 AN: 1097495 Hom.: 0 Cov.: 34 AF XY: 0.00000826 AC XY: 3 AN XY: 363301

African (AFR) AF: 0.00 AC: 0 AN: 26394

American (AMR) AF: 0.00 AC: 0 AN: 35192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19370

East Asian (EAS) AF: 0.00 AC: 0 AN: 30196

South Asian (SAS) AF: 0.00 AC: 0 AN: 54136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40056

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00000475 AC: 4 AN: 841936

Other (OTH) AF: 0.00 AC: 0 AN: 46078

GnomAD4 genome AF: 0.0000356 AC: 4 AN: 112214 Hom.: 0 Cov.: 26 AF XY: 0.0000289 AC XY: 1 AN XY: 34568

African (AFR) AF: 0.00 AC: 0 AN: 30938

American (AMR) AF: 0.00 AC: 0 AN: 10822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3507

South Asian (SAS) AF: 0.000368 AC: 1 AN: 2720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6225

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.0000567 AC: 3 AN: 52926

Other (OTH) AF: 0.00 AC: 0 AN: 1539

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	L
PhyloP100		-1.5
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.026
Sift	Benign	0.18	T
Sift4G	Benign	0.35	T
Polyphen		0.59	P
Vest4		0.035
MutPred		0.23		Gain of methylation at E170 (P = 0.0031)
MVP		0.068
MPC		1.1
ClinPred		0.24	T
GERP RS		1.1
Varity_R		0.050
gMVP		0.32
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1482209977; hg19: chrX-75648831;