NM_002365.5:c.433C>T

Variant names:

• chrX-30236357-C-T
• rs768698062
• NM_002365.5:c.433C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_002365.5(MAGEB3):​c.433C>T​(p.His145Tyr) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: MAGEB3 NM_002365.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.572
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.071953446).
• BP6: Variant X-30236357-C-T is Benign according to our data. Variant chrX-30236357-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3869557.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002365.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEB3	NM_002365.5	MANE Select	c.433C>T	p.His145Tyr	missense	Exon 5 of 5	NP_002356.2
	MAGEB3	NM_001386865.1		c.433C>T	p.His145Tyr	missense	Exon 3 of 3	NP_001373794.1	O15480

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEB3	ENST00000361644.4	TSL:2 MANE Select	c.433C>T	p.His145Tyr	missense	Exon 5 of 5	ENSP00000355198.2	O15480
	MAGEB3	ENST00000620842.1	TSL:6	c.433C>T	p.His145Tyr	missense	Exon 1 of 1	ENSP00000478513.1	O15480

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000556 AC: 1 AN: 179861 AF XY: 0.00

Gnomad AFR exome AF: 0.0000770

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 23

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0020
DANN	Benign	0.20
DEOGEN2	Benign	0.017	T
FATHMM_MKL	Benign	0.00091	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.2	N
PhyloP100		-0.57
PrimateAI	Benign	0.45	T
PROVEAN	Benign	2.6	N
REVEL	Benign	0.074
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.66		Loss of methylation at K143 (P = 0.0703)
MVP		0.043
MPC		0.14
ClinPred		0.011	T
GERP RS		-6.1
PromoterAI		-0.0056	Neutral
Varity_R		0.037
gMVP		0.24
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs768698062; hg19: chrX-30254474;