chrX-30236732-C-A

Variant names:

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

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>A​(p.Arg270Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,210,679 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 18 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. Variant has been reported in ClinVar as Uncertain significance (★). 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 0.00020 (0 hom., 8 hem., cov: 23)
  • Exomes 𝑓: 0.000025 (0 hom. 10 hem.)
• Consequence: MAGEB3 NM_002365.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.057085752).
• BS2: High Hemizygotes in GnomAd4 at 8 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>A	p.Arg270Ser	missense	Exon 5 of 5	NP_002356.2
	MAGEB3	NM_001386865.1		c.808C>A	p.Arg270Ser	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>A	p.Arg270Ser	missense	Exon 5 of 5	ENSP00000355198.2	O15480
	MAGEB3	ENST00000620842.1	TSL:6	c.808C>A	p.Arg270Ser	missense	Exon 1 of 1	ENSP00000478513.1	O15480

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 23 AN: 112572 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000710

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000937

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000545 AC: 10 AN: 183465 AF XY: 0.0000295

Gnomad AFR exome AF: 0.000532

Gnomad AMR exome AF: 0.000109

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 AF: 0.0000255 AC: 28 AN: 1098107 Hom.: 0 Cov.: 32 AF XY: 0.0000275 AC XY: 10 AN XY: 363463

African (AFR) AF: 0.000568 AC: 15 AN: 26401

American (AMR) AF: 0.000199 AC: 7 AN: 35207

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 30204

South Asian (SAS) AF: 0.00 AC: 0 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: 0.00000356 AC: 3 AN: 842002

Other (OTH) AF: 0.0000651 AC: 3 AN: 46094

GnomAD4 genome AF: 0.000204 AC: 23 AN: 112572 Hom.: 0 Cov.: 23 AF XY: 0.000230 AC XY: 8 AN XY: 34718

African (AFR) AF: 0.000710 AC: 22 AN: 30977

American (AMR) AF: 0.0000937 AC: 1 AN: 10674

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3613

South Asian (SAS) AF: 0.00 AC: 0 AN: 2703

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53333

Other (OTH) AF: 0.00 AC: 0 AN: 1517

Alfa AF: 0.000339 Hom.: 2

Bravo AF: 0.000246

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000494 AC: 6

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.20
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.31
DANN	Benign	0.95
DEOGEN2	Benign	0.014	T
FATHMM_MKL	Benign	0.0083	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.51	N
PhyloP100		-2.3
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.037
Sift	Benign	0.19	T
Sift4G	Benign	0.46	T
Polyphen		0.25	B
Vest4		0.077
MVP		0.043
MPC		0.26
ClinPred		0.043	T
GERP RS		-3.3
Varity_R		0.24
gMVP		0.51
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: rs139917714; hg19: chrX-30254849;