X-30219227-A-G

Variant names:

• chrX-30219227-A-G
• rs149245405
• NM_002364.5:c.647A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_002364.5(MAGEB2):​c.647A>G​(p.Asn216Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,209,017 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000011 (0 hom. 4 hem.)
• Consequence: MAGEB2 NM_002364.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.28
• Publications: 1 publications found

Genes affected

MAGEB2 (HGNC:6809): (MAGE family member B2) This gene is a member of the MAGEB gene family. The members of this family have their entire coding sequences located in the last exon, and the encoded proteins show 50 to 68% sequence identity to each other. The promoters and first exons of the MAGEB genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. This gene is localized in the DSS (dosage-sensitive sex reversal) critical region. It is expressed in testis and placenta, and in a significant fraction of tumors of various histological types. The MAGEB genes are clustered on chromosome Xp22-p21. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.36142358).
• BS2: High Hemizygotes in GnomAdExome4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002364.5. 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
	MAGEB2	NM_002364.5	MANE Select	c.647A>G	p.Asn216Ser	missense	Exon 2 of 2	NP_002355.2	O15479

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEB2	ENST00000378988.5	TSL:1 MANE Select	c.647A>G	p.Asn216Ser	missense	Exon 2 of 2	ENSP00000368273.4	O15479

Frequencies

GnomAD3 genomes AF: 0.00000897 AC: 1 AN: 111449 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

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: 0.0000189

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000110 AC: 2 AN: 182177 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: 0.0000246

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 12 AN: 1097568 Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 4 AN XY: 362934

African (AFR) AF: 0.00 AC: 0 AN: 26395

American (AMR) AF: 0.00 AC: 0 AN: 35183

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19382

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 54039

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40518

Middle Eastern (MID) AF: 0.00218 AC: 9 AN: 4137

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841633

Other (OTH) AF: 0.0000434 AC: 2 AN: 46077

GnomAD4 genome AF: 0.00000897 AC: 1 AN: 111449 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33655

African (AFR) AF: 0.00 AC: 0 AN: 30624

American (AMR) AF: 0.00 AC: 0 AN: 10550

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3554

South Asian (SAS) AF: 0.00 AC: 0 AN: 2608

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6034

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

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 53024

Other (OTH) AF: 0.00 AC: 0 AN: 1496

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.00000824 AC: 1

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	0.15
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		2.3
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.075
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.018	D
Polyphen		0.99	D
Vest4		0.23
MVP		0.24
MPC		0.0052
ClinPred		0.95	D
GERP RS		3.3
Varity_R		0.23
gMVP		0.28
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs149245405; hg19: chrX-30237344;