X-30236732-C-T

Variant names:

• chrX-30236732-C-T
• rs139917714
• NM_002365.5:c.808C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002365.5(MAGEB3):​c.808C>T​(p.Arg270Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,210,725 control chromosomes in the GnomAD database, including 2 homozygotes. There are 75 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R270H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00012 (1 hom., 4 hem., cov: 23)
  • Exomes 𝑓: 0.00015 (1 hom. 71 hem.)
• Consequence: MAGEB3 NM_002365.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014868647).
• BS2: High Hemizygotes in GnomAd4 at 4 gene

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.808C>T	p.Arg270Cys	missense	Exon 5 of 5	NP_002356.2
	MAGEB3	NM_001386865.1		c.808C>T	p.Arg270Cys	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.808C>T	p.Arg270Cys	missense	Exon 5 of 5	ENSP00000355198.2	O15480
	MAGEB3	ENST00000620842.1	TSL:6	c.808C>T	p.Arg270Cys	missense	Exon 1 of 1	ENSP00000478513.1	O15480

Frequencies

GnomAD3 genomes AF: 0.000115 AC: 13 AN: 112569 Hom.: 1 Cov.: 23

Gnomad AFR AF: 0.0000646

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00222

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000938

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000300 AC: 55 AN: 183465 AF XY: 0.000412

Gnomad AFR exome AF: 0.000152

Gnomad AMR exome AF: 0.0000729

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000722

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000732

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000146 AC: 160 AN: 1098104 Hom.: 1 Cov.: 32 AF XY: 0.000195 AC XY: 71 AN XY: 363460

African (AFR) AF: 0.0000758 AC: 2 AN: 26401

American (AMR) AF: 0.0000568 AC: 2 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

East Asian (EAS) AF: 0.0000993 AC: 3 AN: 30203

South Asian (SAS) AF: 0.00192 AC: 104 AN: 54144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.0000439 AC: 37 AN: 842001

Other (OTH) AF: 0.000260 AC: 12 AN: 46094

GnomAD4 genome AF: 0.000115 AC: 13 AN: 112621 Hom.: 1 Cov.: 23 AF XY: 0.000115 AC XY: 4 AN XY: 34779

African (AFR) AF: 0.0000644 AC: 2 AN: 31044

American (AMR) AF: 0.00 AC: 0 AN: 10684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3602

South Asian (SAS) AF: 0.00223 AC: 6 AN: 2695

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.0000938 AC: 5 AN: 53326

Other (OTH) AF: 0.00 AC: 0 AN: 1536

Alfa AF: 0.0000261 Hom.: 2

Bravo AF: 0.0000718

ExAC AF: 0.000288 AC: 35

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.66
DANN	Benign	0.89
DEOGEN2	Benign	0.014	T
FATHMM_MKL	Benign	0.0062	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.47	N
PhyloP100		-2.3
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.014
Sift	Benign	0.16	T
Sift4G	Benign	0.24	T
Polyphen		0.15	B
Vest4		0.070
MutPred		0.49		Loss of disorder (P = 0.0377)
MVP		0.043
MPC		0.18
ClinPred		0.031	T
GERP RS		-3.3
Varity_R		0.11
gMVP		0.57
Mutation Taster		=100/0	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: rs139917714; hg19: chrX-30254849; COSMIC: COSV64396848;