NM_021048.5:c.284C>A

Variant names:

• chrX-152135337-G-T
• rs748262488
• NM_021048.5:c.284C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021048.5(MAGEA10):​c.284C>A​(p.Ser95*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000365 in 1,097,312 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000036 (0 hom. 0 hem.)
• Consequence: MAGEA10 NM_021048.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 0 publications found

Genes affected

MAGEA10 (HGNC:6797): (MAGE family member A10) This gene is a member of the MAGEA gene family. The members of this family encode proteins with 50 to 80% sequence identity to each other. The promoters and first exons of the MAGEA genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. The MAGEA genes are clustered at chromosomal location Xq28. They have been implicated in some hereditary disorders, such as dyskeratosis congenita. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream melanoma antigen family A, 5 (MAGEA5) gene.[provided by RefSeq, Oct 2011]

LOC100533997 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021048.5. 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
	MAGEA10	NM_021048.5	MANE Select	c.284C>A	p.Ser95*	stop_gained	Exon 4 of 4	NP_066386.3	P43363
	MAGEA10	NM_001011543.3		c.284C>A	p.Ser95*	stop_gained	Exon 5 of 5	NP_001011543.3	P43363
	MAGEA10	NM_001251828.2		c.284C>A	p.Ser95*	stop_gained	Exon 5 of 5	NP_001238757.2	P43363

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEA10	ENST00000370323.9	TSL:1 MANE Select	c.284C>A	p.Ser95*	stop_gained	Exon 4 of 4	ENSP00000359347.4	P43363
	MAGEA10	ENST00000244096.7	TSL:2	c.284C>A	p.Ser95*	stop_gained	Exon 5 of 5	ENSP00000244096.3	P43363
	MAGEA10	ENST00000444834.6	TSL:3	c.284C>A	p.Ser95*	stop_gained	Exon 5 of 5	ENSP00000406161.2	C9J958

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD2 exomes AF: 0.00000551 AC: 1 AN: 181651 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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000365 AC: 4 AN: 1097312 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 362714

African (AFR) AF: 0.00 AC: 0 AN: 26387

American (AMR) AF: 0.00 AC: 0 AN: 35123

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19317

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30202

South Asian (SAS) AF: 0.0000556 AC: 3 AN: 53913

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40453

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4129

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841742

Other (OTH) AF: 0.00 AC: 0 AN: 46046

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	23
DANN	Benign	0.94
FATHMM_MKL	Benign	0.045	N
PhyloP100		-1.2
Vest4		0.065
GERP RS		-0.96
Mutation Taster		=139/61	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs748262488; hg19: chrX-151303809;