rs1300910346

Variant names:

• chrX-76428613-C-G
• rs1300910346
• NM_020932.3:c.683C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-76428613-C-G
• chrX-76428613-C-T

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.683C>G​(p.Pro228Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000903 in 110,722 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. 15/21 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. P228L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 25)
  • Exomes 𝑓: 0.000019 (0 hom. 10 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAGEE1 NM_020932.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• 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: 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=0.039108038).

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.683C>G	p.Pro228Arg	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.683C>G	p.Pro228Arg	missense	Exon 1 of 1	ENSP00000354912.2	Q9HCI5

Frequencies

GnomAD3 genomes AF: 0.00000903 AC: 1 AN: 110722 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000292

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: 0.0000170 AC: 3 AN: 176498 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000222

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000192 AC: 21 AN: 1096382 Hom.: 0 Cov.: 35 AF XY: 0.0000276 AC XY: 10 AN XY: 362630

African (AFR) AF: 0.00 AC: 0 AN: 26265

American (AMR) AF: 0.00 AC: 0 AN: 35034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19335

East Asian (EAS) AF: 0.000696 AC: 21 AN: 30169

South Asian (SAS) AF: 0.00 AC: 0 AN: 54021

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39682

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841711

Other (OTH) AF: 0.00 AC: 0 AN: 46030

GnomAD4 genome AF: 0.00000903 AC: 1 AN: 110722 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 33378

African (AFR) AF: 0.00 AC: 0 AN: 30395

American (AMR) AF: 0.00 AC: 0 AN: 10714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2623

East Asian (EAS) AF: 0.000292 AC: 1 AN: 3423

South Asian (SAS) AF: 0.00 AC: 0 AN: 2632

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6114

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 234

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52435

Other (OTH) AF: 0.00 AC: 0 AN: 1508

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	4.9
DANN	Benign	0.53
DEOGEN2	Benign	0.0071	T
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.6	L
PhyloP100		-2.3
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.0090
Sift	Uncertain	0.027	D
Sift4G	Benign	0.062	T
Polyphen		0.032	B
Vest4		0.048
MutPred		0.16		Loss of stability (P = 0.0956)
MVP		0.043
MPC		0.35
ClinPred		0.029	T
GERP RS		-2.4
Varity_R		0.058
gMVP		0.26
Mutation Taster		=98/2	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: rs1300910346; hg19: chrX-75649006;