X-30218598-G-C

Variant names:

• chrX-30218598-G-C
• rs1020866755
• NM_002364.5:c.18G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002364.5(MAGEB2):​c.18G>C​(p.Lys6Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000183 in 1,093,884 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: MAGEB2 NM_002364.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24573451).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEB2	NM_002364.5	c.18G>C	p.Lys6Asn	missense_variant	Exon 2 of 2	ENST00000378988.5	NP_002355.2
MAGEB2	XM_011545512.2	c.18G>C	p.Lys6Asn	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.18G>C	p.Lys6Asn	missense_variant	Exon 2 of 2	1	NM_002364.5	ENSP00000368273.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000183 AC: 2 AN: 1093884 Hom.: 0 Cov.: 32 AF XY: 0.00000278 AC XY: 1 AN XY: 359828

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: 0.00000238

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	T
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.12
Sift	Benign	0.047	D
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.35
MutPred		0.34		Loss of methylation at K6 (P = 0.0258);
MVP		0.26
MPC		0.0079
ClinPred		0.99	D
GERP RS		0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.77
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1020866755; hg19: chrX-30236715;