X-27821343-G-A

Position:

• chrX-27821343-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182506.3(MAGEB10):​c.37G>A​(p.Glu13Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,097,743 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: MAGEB10 NM_182506.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.940

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14487007).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEB10	NM_182506.3	c.37G>A	p.Glu13Lys	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.37G>A	p.Glu13Lys	missense_variant	3/3	1	NM_182506.3	ENSP00000368304	P1
MAGEB10	ENST00000614159.1	c.37G>A	p.Glu13Lys	missense_variant	1/1			ENSP00000480889	P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097743 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 363131

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000568

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

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

Mar 07, 2024

The c.37G>A (p.E13K) 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 37, causing the glutamic acid (E) at amino acid position 13 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	0.21
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T;T
FATHMM_MKL	Benign	0.039	N
LIST_S2	Uncertain	0.88	.;D
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.6	D;.
REVEL	Benign	0.013
Sift	Benign	0.033	D;.
Sift4G	Benign	0.087	T;T
Polyphen		0.96	D;D
Vest4		0.16
MutPred		0.37		Gain of ubiquitination at E13 (P = 0.1008);Gain of ubiquitination at E13 (P = 0.1008);
MVP		0.10
MPC		0.75
ClinPred		0.81	D
GERP RS		0.69
Varity_R		0.41
gMVP		0.40

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-27839460; COSMIC: COSV63311597;