chrX-76428412-G-C

Variant names:

• chrX-76428412-G-C
• NM_020932.3:c.482G>C

Variant summary

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

The NM_020932.3(MAGEE1):​c.482G>C​(p.Ser161Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,728 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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: MAGEE1 NM_020932.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159

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=0.0677551).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEE1	NM_020932.3	c.482G>C	p.Ser161Thr	missense_variant	Exon 1 of 1	ENST00000361470.4	NP_065983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGEE1	ENST00000361470.4	c.482G>C	p.Ser161Thr	missense_variant	Exon 1 of 1	6	NM_020932.3	ENSP00000354912.2

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1096728 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 363162

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	5.1
DANN	Benign	0.19
DEOGEN2	Benign	0.0069	T
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.031
Sift	Uncertain	0.024	D
Sift4G	Benign	0.29	T
Polyphen		0.20	B
Vest4		0.027
MutPred		0.18		Gain of glycosylation at P166 (P = 0.207);
MVP		0.043
MPC		0.34
ClinPred		0.057	T
GERP RS		-0.0012
Varity_R		0.075
gMVP		0.19

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-75648805;