rs1924487974

Variant names:

• chrX-30219073-G-C
• rs1924487974
• NM_002364.5:c.493G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-30219073-G-C
• chrX-30219073-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_002364.5(MAGEB2):​c.493G>C​(p.Gly165Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: MAGEB2 NM_002364.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.95

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_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.989

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEB2	NM_002364.5	c.493G>C	p.Gly165Arg	missense_variant	Exon 2 of 2	ENST00000378988.5	NP_002355.2
MAGEB2	XM_011545512.2	c.493G>C	p.Gly165Arg	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.493G>C	p.Gly165Arg	missense_variant	Exon 2 of 2	1	NM_002364.5	ENSP00000368273.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 111991 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34171 FAILED QC

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 111991 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34171

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: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0097	T
MetaRNN	Pathogenic	0.99	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Pathogenic	3.8	H
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-8.0	D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.97		Gain of ubiquitination at K170 (P = 0.0671);
MVP		0.45
MPC		0.0078
ClinPred		1.0	D
GERP RS		2.4
Varity_R		0.83
gMVP		0.82

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: rs1924487974; hg19: chrX-30237190;