X-30236213-T-C

Variant names:

• chrX-30236213-T-C
• rs780480082
• NM_002365.5:c.289T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_002365.5(MAGEB3):​c.289T>C​(p.Ser97Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000381 in 1,208,796 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.000040 (0 hom. 16 hem.)
• Consequence: MAGEB3 NM_002365.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.900
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.105044246).
• BS2: High Hemizygotes in GnomAdExome4 at 16 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.289T>C	p.Ser97Pro	missense	Exon 5 of 5	NP_002356.2
	MAGEB3	NM_001386865.1		c.289T>C	p.Ser97Pro	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.289T>C	p.Ser97Pro	missense	Exon 5 of 5	ENSP00000355198.2	O15480
	MAGEB3	ENST00000620842.1	TSL:6	c.289T>C	p.Ser97Pro	missense	Exon 1 of 1	ENSP00000478513.1	O15480

Frequencies

GnomAD3 genomes AF: 0.0000180 AC: 2 AN: 111401 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000327

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000276 AC: 5 AN: 181148 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.0000619

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000401 AC: 44 AN: 1097395 Hom.: 0 Cov.: 30 AF XY: 0.0000441 AC XY: 16 AN XY: 362779

African (AFR) AF: 0.00 AC: 0 AN: 26379

American (AMR) AF: 0.00 AC: 0 AN: 35134

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19363

East Asian (EAS) AF: 0.00 AC: 0 AN: 30199

South Asian (SAS) AF: 0.00 AC: 0 AN: 53973

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40455

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4127

European-Non Finnish (NFE) AF: 0.0000451 AC: 38 AN: 841704

Other (OTH) AF: 0.000130 AC: 6 AN: 46061

GnomAD4 genome AF: 0.0000180 AC: 2 AN: 111401 Hom.: 0 Cov.: 22 AF XY: 0.0000298 AC XY: 1 AN XY: 33613

African (AFR) AF: 0.0000327 AC: 1 AN: 30568

American (AMR) AF: 0.00 AC: 0 AN: 10555

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2633

East Asian (EAS) AF: 0.00 AC: 0 AN: 3544

South Asian (SAS) AF: 0.00 AC: 0 AN: 2600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6006

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

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53071

Other (OTH) AF: 0.00 AC: 0 AN: 1506

Alfa AF: 0.000130 Hom.: 1

Bravo AF: 0.0000151

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000330 AC: 4

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	0.072
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.3
DANN	Benign	0.97
DEOGEN2	Benign	0.074	T
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.90
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.11
Sift	Benign	0.089	T
Sift4G	Benign	0.063	T
Polyphen		0.23	B
Vest4		0.25
MutPred		0.25		Loss of phosphorylation at S97 (P = 0.0354)
MVP		0.068
MPC		0.24
ClinPred		0.13	T
GERP RS		0.0086
PromoterAI		0.0071	Neutral
Varity_R		0.27
gMVP		0.080
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: rs780480082; hg19: chrX-30254330;