X-27821448-G-T

Position:

• chrX-27821448-G-T

Variant summary

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

The ENST00000356790.2(MAGEB10):​c.142G>T​(p.Asp48Tyr) 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 1,098,112 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. 12/20 in silico tools predict 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 ENST00000356790.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.761

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=0.14389679).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEB10	NM_182506.3	c.142G>T	p.Asp48Tyr	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.142G>T	p.Asp48Tyr	missense_variant	3/3	1	NM_182506.3	ENSP00000368304.1
MAGEB10	ENST00000614159.1	c.142G>T	p.Asp48Tyr	missense_variant	1/1	6		ENSP00000480889.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1098112 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 363470

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000238

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

Jun 24, 2022

The c.142G>T (p.D48Y) alteration is located in exon 3 (coding exon 1) of the MAGEB10 gene. This alteration results from a G to T substitution at nucleotide position 142, causing the aspartic acid (D) at amino acid position 48 to be replaced by a tyrosine (Y). 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	0.11
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	14
DANN	Benign	0.91
DEOGEN2	Benign	0.059	T;T
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.30	.;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-2.9	D;.
REVEL	Benign	0.057
Sift	Benign	0.80	T;.
Sift4G	Uncertain	0.022	D;D
Polyphen		0.98	D;D
Vest4		0.13
MutPred		0.46		Loss of helix (P = 0.028);Loss of helix (P = 0.028);
MVP		0.093
MPC		0.56
ClinPred		0.34	T
GERP RS		2.4
Varity_R		0.21
gMVP		0.28

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-27839565;