X-76427989-C-G

Variant names:

• chrX-76427989-C-G
• rs782197127
• NM_020932.3:c.59C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020932.3(MAGEE1):​c.59C>G​(p.Ala20Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000166 in 1,205,511 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A20V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 25)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: MAGEE1 NM_020932.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040345907).

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.59C>G	p.Ala20Gly	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.59C>G	p.Ala20Gly	missense	Exon 1 of 1	ENSP00000354912.2	Q9HCI5

Frequencies

GnomAD3 genomes AF: 0.00000886 AC: 1 AN: 112929 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.0000322

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD4 exome AF: 9.15e-7 AC: 1 AN: 1092582 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 359066

African (AFR) AF: 0.00 AC: 0 AN: 26340

American (AMR) AF: 0.00 AC: 0 AN: 34600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19169

East Asian (EAS) AF: 0.00 AC: 0 AN: 30083

South Asian (SAS) AF: 0.00 AC: 0 AN: 53163

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3772

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 839999

Other (OTH) AF: 0.00 AC: 0 AN: 45798

GnomAD4 genome AF: 0.00000886 AC: 1 AN: 112929 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 35079

African (AFR) AF: 0.0000322 AC: 1 AN: 31103

American (AMR) AF: 0.00 AC: 0 AN: 10780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2659

East Asian (EAS) AF: 0.00 AC: 0 AN: 3561

South Asian (SAS) AF: 0.00 AC: 0 AN: 2778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6263

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53349

Other (OTH) AF: 0.00 AC: 0 AN: 1517

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.012	T
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.2	L
PhyloP100		-2.0
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.060
Sift	Benign	0.053	T
Sift4G	Benign	0.55	T
Polyphen		0.0020	B
Vest4		0.042
MutPred		0.14		Loss of stability (P = 0.0767)
MVP		0.043
MPC		0.32
ClinPred		0.040	T
GERP RS		-2.8
PromoterAI		-0.0067	Neutral
Varity_R		0.060
gMVP		0.24
Mutation Taster		=100/0	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: rs782197127; hg19: chrX-75648382;