chrX-152134849-C-T

Variant names:

• chrX-152134849-C-T
• NM_021048.5:c.772G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021048.5(MAGEA10):​c.772G>A​(p.Gly258Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: MAGEA10 NM_021048.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.49

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEA10	NM_021048.5	c.772G>A	p.Gly258Arg	missense_variant	Exon 4 of 4	ENST00000370323.9	NP_066386.3
MAGEA10	NM_001011543.3	c.772G>A	p.Gly258Arg	missense_variant	Exon 5 of 5		NP_001011543.3
MAGEA10	NM_001251828.2	c.772G>A	p.Gly258Arg	missense_variant	Exon 5 of 5		NP_001238757.2
LOC100533997	NM_001204811.3	c.-278+3626G>A		intron_variant	Intron 1 of 3		NP_001191740.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGEA10	ENST00000370323.9	c.772G>A	p.Gly258Arg	missense_variant	Exon 4 of 4	1	NM_021048.5	ENSP00000359347.4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.772G>A (p.G258R) alteration is located in exon 5 (coding exon 1) of the MAGEA10 gene. This alteration results from a G to A substitution at nucleotide position 772, causing the glycine (G) at amino acid position 258 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T;T
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.82	.;T
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-7.5	D;D
REVEL	Benign	0.047
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;D
Vest4		0.20
MutPred		0.80		Gain of solvent accessibility (P = 0.0456);Gain of solvent accessibility (P = 0.0456);
MVP		0.21
MPC		0.48
ClinPred		0.99	D
GERP RS		2.6
Varity_R		0.47
gMVP		0.59

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-151303321;