rs782793836

Variant names:

• chrX-76428316-C-G
• rs782793836
• NM_020932.3:c.386C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-76428316-C-G
• chrX-76428316-C-T

Variant summary

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

The NM_020932.3(MAGEE1):​c.386C>G​(p.Thr129Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,209,236 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T129M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 3 hem., cov: 26)
  • Exomes 𝑓: 0.000020 (0 hom. 7 hem.)
• Consequence: MAGEE1 NM_020932.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.351
• 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=0.011448592).
• BS2: High Hemizygotes in GnomAd4 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.386C>G	p.Thr129Arg	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.386C>G	p.Thr129Arg	missense	Exon 1 of 1	ENSP00000354912.2	Q9HCI5

Frequencies

GnomAD3 genomes AF: 0.0000449 AC: 5 AN: 111372 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000933

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00115

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

GnomAD2 exomes AF: 0.000116 AC: 21 AN: 180897 AF XY: 0.000121

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00153

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000200 AC: 22 AN: 1097864 Hom.: 0 Cov.: 33 AF XY: 0.0000193 AC XY: 7 AN XY: 363408

African (AFR) AF: 0.00 AC: 0 AN: 26401

American (AMR) AF: 0.00 AC: 0 AN: 35194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19374

East Asian (EAS) AF: 0.000662 AC: 20 AN: 30203

South Asian (SAS) AF: 0.00 AC: 0 AN: 54132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40262

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

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 842072

Other (OTH) AF: 0.0000217 AC: 1 AN: 46089

GnomAD4 genome AF: 0.0000449 AC: 5 AN: 111372 Hom.: 0 Cov.: 26 AF XY: 0.0000885 AC XY: 3 AN XY: 33890

African (AFR) AF: 0.00 AC: 0 AN: 30577

American (AMR) AF: 0.0000933 AC: 1 AN: 10717

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2637

East Asian (EAS) AF: 0.00115 AC: 4 AN: 3486

South Asian (SAS) AF: 0.00 AC: 0 AN: 2681

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6115

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 229

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52756

Other (OTH) AF: 0.00 AC: 0 AN: 1502

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.0000741 AC: 9

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	0.12
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.98
CADD	Benign	11
DANN	Benign	0.90
DEOGEN2	Benign	0.0097	T
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.35
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.68	N
REVEL	Benign	0.0030
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.072	T
Polyphen		0.22	B
Vest4		0.075
MutPred		0.32		Gain of MoRF binding (P = 0.0045)
MVP		0.043
MPC		0.40
ClinPred		0.035	T
GERP RS		1.3
Varity_R		0.11
gMVP		0.24
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: rs782793836; hg19: chrX-75648709;