X-149885036-AG-GA

Variant names:

• chrX-149885036-AG-GA
• NM_005364.5:c.764_765delAGinsGA
• MAGEA8 p.Gln255Arg

Variant summary

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

The NM_005364.5(MAGEA8):​c.764_765delAGinsGA​(p.Gln255Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 24)
• Consequence: MAGEA8 NM_005364.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433
• Publications: 0 publications found

Genes affected

MAGEA8 (HGNC:6806): (MAGE family member A8) 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. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Oct 2009]

MAGEA8-AS1 (HGNC:45093): (MAGEA8 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005364.5. 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
	MAGEA8	NM_005364.5	MANE Select	c.764_765delAGinsGA	p.Gln255Arg	missense	N/A	NP_005355.2
	MAGEA8	NM_001166400.2		c.764_765delAGinsGA	p.Gln255Arg	missense	N/A	NP_001159872.1	P43361
	MAGEA8	NM_001166401.2		c.764_765delAGinsGA	p.Gln255Arg	missense	N/A	NP_001159873.1	P43361

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEA8	ENST00000286482.6	TSL:1 MANE Select	c.764_765delAGinsGA	p.Gln255Arg	missense	N/A	ENSP00000286482.1	P43361
	MAGEA8	ENST00000535454.5	TSL:3	c.764_765delAGinsGA	p.Gln255Arg	missense	N/A	ENSP00000438293.1	P43361
	MAGEA8	ENST00000542674.5	TSL:3	c.764_765delAGinsGA	p.Gln255Arg	missense	N/A	ENSP00000443776.1	P43361

Frequencies

GnomAD3 genomes Cov.: 24

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-149013810;