chrX-30235947-C-T

Variant names:

• chrX-30235947-C-T
• rs201131077
• NM_002365.5:c.23C>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.23C>T​(p.Thr8Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,204,830 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 45 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T8A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., 6 hem., cov: 22)
  • Exomes 𝑓: 0.00012 (0 hom. 39 hem.)
• Consequence: MAGEB3 NM_002365.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.105
• 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=0.03599748).
• BS2: High Hemizygotes in GnomAd4 at 6 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.23C>T	p.Thr8Met	missense	Exon 5 of 5	NP_002356.2
	MAGEB3	NM_001386865.1		c.23C>T	p.Thr8Met	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.23C>T	p.Thr8Met	missense	Exon 5 of 5	ENSP00000355198.2	O15480
	MAGEB3	ENST00000620842.1	TSL:6	c.23C>T	p.Thr8Met	missense	Exon 1 of 1	ENSP00000478513.1	O15480

Frequencies

GnomAD3 genomes AF: 0.000126 AC: 14 AN: 111350 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: 0.00132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000755

Gnomad OTH AF: 0.000674

GnomAD2 exomes AF: 0.000120 AC: 21 AN: 175066 AF XY: 0.0000995

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: 0.000578

Gnomad NFE exome AF: 0.000102

Gnomad OTH exome AF: 0.000699

GnomAD4 exome AF: 0.000120 AC: 131 AN: 1093480 Hom.: 0 Cov.: 30 AF XY: 0.000108 AC XY: 39 AN XY: 359622

African (AFR) AF: 0.00 AC: 0 AN: 26287

American (AMR) AF: 0.00 AC: 0 AN: 34763

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19005

East Asian (EAS) AF: 0.00 AC: 0 AN: 30190

South Asian (SAS) AF: 0.0000189 AC: 1 AN: 52982

European-Finnish (FIN) AF: 0.000892 AC: 36 AN: 40364

Middle Eastern (MID) AF: 0.000244 AC: 1 AN: 4103

European-Non Finnish (NFE) AF: 0.0000976 AC: 82 AN: 839864

Other (OTH) AF: 0.000240 AC: 11 AN: 45922

GnomAD4 genome AF: 0.000126 AC: 14 AN: 111350 Hom.: 0 Cov.: 22 AF XY: 0.000179 AC XY: 6 AN XY: 33536

African (AFR) AF: 0.0000327 AC: 1 AN: 30574

American (AMR) AF: 0.00 AC: 0 AN: 10528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2644

East Asian (EAS) AF: 0.00 AC: 0 AN: 3539

South Asian (SAS) AF: 0.00 AC: 0 AN: 2578

European-Finnish (FIN) AF: 0.00132 AC: 8 AN: 6076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000755 AC: 4 AN: 53011

Other (OTH) AF: 0.000674 AC: 1 AN: 1484

Alfa AF: 0.0000943 Hom.: 3

Bravo AF: 0.0000340

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

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	0.097
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0037	T
FATHMM_MKL	Benign	0.013	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.10
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.075
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.97	D
Vest4		0.11
MVP		0.043
MPC		0.13
ClinPred		0.32	T
GERP RS		-1.8
PromoterAI		0.0044	Neutral
Varity_R		0.058
gMVP		0.17
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: rs201131077; hg19: chrX-30254064; COSMIC: COSV100854631;