X-76428051-C-G

Position:

• chrX-76428051-C-G

Variant summary

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

The NM_020932.3(MAGEE1):​c.121C>G​(p.Pro41Ala) 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: 25)
• Consequence: MAGEE1 NM_020932.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.847

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=0.046652764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEE1	NM_020932.3	c.121C>G	p.Pro41Ala	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.121C>G	p.Pro41Ala	missense_variant	1/1	6	NM_020932.3	ENSP00000354912.2

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 25

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

Apr 15, 2024

The c.121C>G (p.P41A) alteration is located in exon 1 (coding exon 1) of the MAGEE1 gene. This alteration results from a C to G substitution at nucleotide position 121, causing the proline (P) at amino acid position 41 to be replaced by an alanine (A). 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	0.067
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.46
DANN	Benign	0.76
DEOGEN2	Benign	0.018	T
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.031
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.035	D
Polyphen		0.0	B
Vest4		0.055
MutPred		0.15		Gain of catalytic residue at P41 (P = 0.2547);
MVP		0.043
MPC		0.30
ClinPred		0.063	T
GERP RS		-1.1
Varity_R		0.041
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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-75648444;