X-30236363-A-G

Variant names:

• chrX-30236363-A-G
• rs1924981057
• NM_002365.5:c.439A>G

Variant summary

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

The NM_002365.5(MAGEB3):​c.439A>G​(p.Asn147Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,096,357 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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 (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000055 (0 hom. 3 hem.)
• Consequence: MAGEB3 NM_002365.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.404
• Publications: 0 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=0.05504355).
• BS2: High Hemizygotes in GnomAdExome4 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.439A>G	p.Asn147Asp	missense	Exon 5 of 5	NP_002356.2
	MAGEB3	NM_001386865.1		c.439A>G	p.Asn147Asp	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.439A>G	p.Asn147Asp	missense	Exon 5 of 5	ENSP00000355198.2	O15480
	MAGEB3	ENST00000620842.1	TSL:6	c.439A>G	p.Asn147Asp	missense	Exon 1 of 1	ENSP00000478513.1	O15480

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000547 AC: 6 AN: 1096357 Hom.: 0 Cov.: 34 AF XY: 0.00000829 AC XY: 3 AN XY: 361845

African (AFR) AF: 0.0000759 AC: 2 AN: 26349

American (AMR) AF: 0.00 AC: 0 AN: 34983

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19335

East Asian (EAS) AF: 0.00 AC: 0 AN: 30201

South Asian (SAS) AF: 0.0000187 AC: 1 AN: 53541

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40509

Middle Eastern (MID) AF: 0.000243 AC: 1 AN: 4119

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841271

Other (OTH) AF: 0.0000434 AC: 2 AN: 46049

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

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	0.093
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.047
DANN	Benign	0.43
DEOGEN2	Benign	0.0011	T
FATHMM_MKL	Benign	0.0089	N
LIST_S2	Benign	0.042	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.28	N
PhyloP100		-0.40
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.012
Sift	Benign	0.66	T
Sift4G	Benign	0.65	T
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.51		Loss of MoRF binding (P = 0.0444)
MVP		0.068
MPC		0.14
ClinPred		0.037	T
GERP RS		-3.3
PromoterAI		-0.0055	Neutral
Varity_R		0.062
gMVP		0.11
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: rs1924981057; hg19: chrX-30254480;