X-27821967-G-A

Position:

• chrX-27821967-G-A

Variant summary

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

The NM_182506.3(MAGEB10):​c.661G>A​(p.Glu221Lys) 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: 23)
• Consequence: MAGEB10 NM_182506.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0460

Genes affected

MAGEB10 (HGNC:25377): (MAGE family member B10) This gene encodes a member of the B subfamily of the melanoma associated antigen protein family. The encoded protein is specifically expressed in testis and tumor cells. [provided by RefSeq, Apr 2010]

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/exons	MANE	Protein	UniProt
MAGEB10	NM_182506.3	c.661G>A	p.Glu221Lys	missense_variant	3/3	ENST00000356790.2	NP_872312.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEB10	ENST00000356790.2	c.661G>A	p.Glu221Lys	missense_variant	3/3	1	NM_182506.3	ENSP00000368304	P1
MAGEB10	ENST00000614159.1	c.661G>A	p.Glu221Lys	missense_variant	1/1			ENSP00000480889	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 16, 2024

The c.661G>A (p.E221K) alteration is located in exon 3 (coding exon 1) of the MAGEB10 gene. This alteration results from a G to A substitution at nucleotide position 661, causing the glutamic acid (E) at amino acid position 221 to be replaced by a lysine (K). 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	Benign	0.15
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T;T
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.77	.;T
M_CAP	Benign	0.0030	T
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M;M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.8	D;.
REVEL	Benign	0.094
Sift	Uncertain	0.028	D;.
Sift4G	Uncertain	0.017	D;D
Polyphen		0.98	D;D
Vest4		0.20
MutPred		0.74		Gain of methylation at E221 (P = 0.0294);Gain of methylation at E221 (P = 0.0294);
MVP		0.15
MPC		0.91
ClinPred		0.94	D
GERP RS		2.6
Varity_R		0.21
gMVP		0.62

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-27840084;