X-30242833-A-G

Position:

• chrX-30242833-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002367.4(MAGEB4):​c.698A>G​(p.Lys233Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: MAGEB4 NM_002367.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.29

Genes affected

MAGEB4 (HGNC:6811): (MAGE family member B4) 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. The MAGEB genes are clustered on chromosome Xp22-p21. This gene sequence ends in the first intron of MAGEB1, another family member. This gene is expressed in testis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04450202).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEB4	NM_002367.4	c.698A>G	p.Lys233Arg	missense_variant	1/1	ENST00000378982.4	NP_002358.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEB4	ENST00000378982.4	c.698A>G	p.Lys233Arg	missense_variant	1/1		NM_002367.4	ENSP00000368266	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.698A>G (p.K233R) alteration is located in exon 1 (coding exon 1) of the MAGEB4 gene. This alteration results from a A to G substitution at nucleotide position 698, causing the lysine (K) at amino acid position 233 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.037
DANN	Benign	0.33
DEOGEN2	Benign	0.013	T
FATHMM_MKL	Benign	0.0028	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.43	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.049
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.055	B
Vest4		0.048
MutPred		0.47		Loss of methylation at K233 (P = 0.0268);
MVP		0.14
MPC		0.14
ClinPred		0.094	T
GERP RS		-6.3
Varity_R		0.047
gMVP		0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-30260950;