X-76428718-C-A

Variant names:

• chrX-76428718-C-A
• rs782462522
• NM_020932.3:c.788C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020932.3(MAGEE1):​c.788C>A​(p.Thr263Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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: 9.1e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAGEE1 NM_020932.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.313
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.085458696).

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.788C>A	p.Thr263Asn	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.788C>A	p.Thr263Asn	missense	Exon 1 of 1	ENSP00000354912.2	Q9HCI5

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD2 exomes AF: 0.00000553 AC: 1 AN: 180833 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000125

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.11e-7 AC: 1 AN: 1097311 Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 1 AN XY: 363221

African (AFR) AF: 0.00 AC: 0 AN: 26390

American (AMR) AF: 0.00 AC: 0 AN: 35137

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19357

East Asian (EAS) AF: 0.00 AC: 0 AN: 30187

South Asian (SAS) AF: 0.00 AC: 0 AN: 54119

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39913

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841996

Other (OTH) AF: 0.0000217 AC: 1 AN: 46076

GnomAD4 genome Cov.: 26

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000165 AC: 2

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	0.11
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.96
CADD	Benign	13
DANN	Benign	0.89
DEOGEN2	Benign	0.014	T
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.31
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.040
Sift	Uncertain	0.011	D
Sift4G	Benign	0.092	T
Polyphen		0.60	P
Vest4		0.085
MutPred		0.20		Loss of phosphorylation at T263 (P = 0.0018)
MVP		0.043
MPC		0.36
ClinPred		0.035	T
GERP RS		0.054
Varity_R		0.076
gMVP		0.19
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs782462522; hg19: chrX-75649111;