X-30218647-C-G

Variant names:

• chrX-30218647-C-G
• rs369826731
• NM_002364.5:c.67C>G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_002364.5(MAGEB2):​c.67C>G​(p.Arg23Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000091 in 1,209,205 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000091 (0 hom. 5 hem.)
• Consequence: MAGEB2 NM_002364.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414

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

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06839728).
• BS2: High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEB2	NM_002364.5	c.67C>G	p.Arg23Gly	missense_variant	Exon 2 of 2	ENST00000378988.5	NP_002355.2
MAGEB2	XM_011545512.2	c.67C>G	p.Arg23Gly	missense_variant	Exon 2 of 2		XP_011543814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGEB2	ENST00000378988.5	c.67C>G	p.Arg23Gly	missense_variant	Exon 2 of 2	1	NM_002364.5	ENSP00000368273.4

Frequencies

GnomAD3 genomes AF: 0.00000891 AC: 1 AN: 112218 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34382

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000912 AC: 10 AN: 1096987 Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 5 AN XY: 362371

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000891 AC: 1 AN: 112218 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34382

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	13
DANN	Benign	0.92
DEOGEN2	Benign	0.016	T
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.14	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.20	N
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.020
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.022	D
Polyphen		0.042	B
Vest4		0.10
MVP		0.20
MPC		0.0024
ClinPred		0.090	T
GERP RS		2.5
Varity_R		0.18
gMVP		0.14

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

Publications

LitVar

Other links and lift over

dbSNP: rs369826731; hg19: chrX-30236764;