X-30236022-C-A

Position:

• chrX-30236022-C-A

Variant summary

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

The NM_002365.5(MAGEB3):​c.98C>A​(p.Thr33Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 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)
• Consequence: MAGEB3 NM_002365.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.528

Genes affected

MAGEB3 (HGNC:6810): (MAGE family member B3) This gene is a MAGE-B subfamily member of the MAGE gene family. MAGE family member proteins direct the expression of tumor antigens recognized on a human melanoma by autologous cytolytic T lymphocytes. There are two known clusters of MAGE genes on chromosome X. The members of the MAGE-A subfamily are located in the Xq28 region, while the members of the MAGE-B subfamily are clustered in the Xp21 region. [provided by RefSeq, Jul 2008]

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=0.14585137).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEB3	NM_002365.5	c.98C>A	p.Thr33Asn	missense_variant	5/5	ENST00000361644.4	NP_002356.2
MAGEB3	NM_001386865.1	c.98C>A	p.Thr33Asn	missense_variant	3/3		NP_001373794.1
MAGEB3	XM_011545513.3	c.98C>A	p.Thr33Asn	missense_variant	4/4		XP_011543815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEB3	ENST00000361644.4	c.98C>A	p.Thr33Asn	missense_variant	5/5	2	NM_002365.5	ENSP00000355198	P1
MAGEB3	ENST00000620842.1	c.98C>A	p.Thr33Asn	missense_variant	1/1			ENSP00000478513	P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

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

Feb 26, 2024

The c.98C>A (p.T33N) alteration is located in exon 5 (coding exon 1) of the MAGEB3 gene. This alteration results from a C to A substitution at nucleotide position 98, causing the threonine (T) at amino acid position 33 to be replaced by an asparagine (N). 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	0.096
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.014	T;T
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.19	.;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.8	D;.
REVEL	Benign	0.085
Sift	Benign	0.034	D;.
Sift4G	Uncertain	0.047	D;D
Polyphen		1.0	D;D
Vest4		0.038
MutPred		0.20		Loss of stability (P = 0.0956);Loss of stability (P = 0.0956);
MVP		0.19
MPC		0.17
ClinPred		0.39	T
GERP RS		1.9
Varity_R		0.14
gMVP		0.12

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-30254139;