X-76428924-G-A

Position:

• chrX-76428924-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020932.3(MAGEE1):​c.994G>A​(p.Val332Met) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 27)
• Consequence: MAGEE1 NM_020932.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.06

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05226794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEE1	NM_020932.3	c.994G>A	p.Val332Met	missense_variant	1/1	ENST00000361470.4	NP_065983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEE1	ENST00000361470.4	c.994G>A	p.Val332Met	missense_variant	1/1	6	NM_020932.3	ENSP00000354912.2

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 27

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 26, 2023

The c.994G>A (p.V332M) alteration is located in exon 1 (coding exon 1) of the MAGEE1 gene. This alteration results from a G to A substitution at nucleotide position 994, causing the valine (V) at amino acid position 332 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	3.3
DANN	Benign	0.89
DEOGEN2	Benign	0.017	T
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.049
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.056	T
Polyphen		0.023	B
Vest4		0.067
MutPred		0.17		Gain of glycosylation at P333 (P = 0.1059);
MVP		0.082
MPC		0.49
ClinPred		0.073	T
GERP RS		-3.9
Varity_R		0.053
gMVP		0.085

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-75649317;