chrX-30236867-G-A

Variant names:

• chrX-30236867-G-A
• rs373510571
• NM_002365.5:c.943G>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.943G>A​(p.Glu315Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000901 in 1,210,081 control chromosomes in the GnomAD database, including 1 homozygotes. There are 24 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., 3 hem., cov: 24)
  • Exomes 𝑓: 0.000076 (1 hom. 21 hem.)
• Consequence: MAGEB3 NM_002365.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.13
• 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=0.008831173).
• BS2: High Hemizygotes in GnomAd4 at 3 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.943G>A	p.Glu315Lys	missense	Exon 5 of 5	NP_002356.2
	MAGEB3	NM_001386865.1		c.943G>A	p.Glu315Lys	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.943G>A	p.Glu315Lys	missense	Exon 5 of 5	ENSP00000355198.2	O15480
	MAGEB3	ENST00000620842.1	TSL:6	c.943G>A	p.Glu315Lys	missense	Exon 1 of 1	ENSP00000478513.1	O15480

Frequencies

GnomAD3 genomes AF: 0.000232 AC: 26 AN: 112165 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000227

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00112

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000660

GnomAD2 exomes AF: 0.000158 AC: 29 AN: 183354 AF XY: 0.0000737

Gnomad AFR exome AF: 0.000304

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00152

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.000663

GnomAD4 exome AF: 0.0000756 AC: 83 AN: 1097862 Hom.: 1 Cov.: 32 AF XY: 0.0000578 AC XY: 21 AN XY: 363216

African (AFR) AF: 0.000189 AC: 5 AN: 26391

American (AMR) AF: 0.00 AC: 0 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19384

East Asian (EAS) AF: 0.000861 AC: 26 AN: 30204

South Asian (SAS) AF: 0.00 AC: 0 AN: 54133

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 841793

Other (OTH) AF: 0.00108 AC: 50 AN: 46088

GnomAD4 genome AF: 0.000232 AC: 26 AN: 112219 Hom.: 0 Cov.: 24 AF XY: 0.0000872 AC XY: 3 AN XY: 34403

African (AFR) AF: 0.000226 AC: 7 AN: 30930

American (AMR) AF: 0.00132 AC: 14 AN: 10627

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

East Asian (EAS) AF: 0.00112 AC: 4 AN: 3573

South Asian (SAS) AF: 0.00 AC: 0 AN: 2666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6094

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53243

Other (OTH) AF: 0.000652 AC: 1 AN: 1534

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.000140

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000132 AC: 16

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	0.075
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.79
DANN	Benign	0.89
DEOGEN2	Benign	0.065	T
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.0088	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.3	L
PhyloP100		-1.1
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.019
Sift	Benign	0.053	T
Sift4G	Benign	0.069	T
Polyphen		0.0060	B
Vest4		0.14
MVP		0.082
MPC		0.13
ClinPred		0.0062	T
GERP RS		-3.1
Varity_R		0.16
gMVP		0.49
Mutation Taster		=98/2	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: rs373510571; hg19: chrX-30254984;