X-30236454-C-T

Variant names:

• chrX-30236454-C-T
• NM_002365.5:c.530C>T

Variant summary

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

The NM_002365.5(MAGEB3):​c.530C>T​(p.Ser177Phe) 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: 24)
• Consequence: MAGEB3 NM_002365.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.335

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 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
MAGEB3	NM_002365.5	c.530C>T	p.Ser177Phe	missense_variant	Exon 5 of 5	ENST00000361644.4	NP_002356.2
MAGEB3	NM_001386865.1	c.530C>T	p.Ser177Phe	missense_variant	Exon 3 of 3		NP_001373794.1
MAGEB3	XM_011545513.3	c.530C>T	p.Ser177Phe	missense_variant	Exon 4 of 4		XP_011543815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGEB3	ENST00000361644.4	c.530C>T	p.Ser177Phe	missense_variant	Exon 5 of 5	2	NM_002365.5	ENSP00000355198.2
MAGEB3	ENST00000620842.1	c.530C>T	p.Ser177Phe	missense_variant	Exon 1 of 1	6		ENSP00000478513.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 23, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.530C>T (p.S177F) alteration is located in exon 5 (coding exon 1) of the MAGEB3 gene. This alteration results from a C to T substitution at nucleotide position 530, causing the serine (S) at amino acid position 177 to be replaced by a phenylalanine (F). 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	0.16
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.80
DEOGEN2	Benign	0.023	T;T
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.10	.;T
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-5.1	D;.
REVEL	Benign	0.20
Sift	Benign	0.66	T;.
Sift4G	Benign	0.67	T;T
Polyphen		0.99	D;D
Vest4		0.16
MutPred		0.61		Gain of catalytic residue at S177 (P = 0.0018);Gain of catalytic residue at S177 (P = 0.0018);
MVP		0.21
MPC		0.40
ClinPred		0.41	T
GERP RS		2.5
Varity_R		0.18
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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-30254571;