X-30219110-C-G

Position:

• chrX-30219110-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_002364.5(MAGEB2):​c.530C>G​(p.Thr177Ser) 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: MAGEB2 NM_002364.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0320

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15297467).
• BP6: Variant X-30219110-C-G is Benign according to our data. Variant chrX-30219110-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2251270.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEB2	NM_002364.5	c.530C>G	p.Thr177Ser	missense_variant	2/2	ENST00000378988.5	NP_002355.2
MAGEB2	XM_011545512.2	c.530C>G	p.Thr177Ser	missense_variant	2/2		XP_011543814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEB2	ENST00000378988.5	c.530C>G	p.Thr177Ser	missense_variant	2/2	1	NM_002364.5	ENSP00000368273.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.19
DANN	Benign	0.25
DEOGEN2	Benign	0.0021	T
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.97	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.92	N
REVEL	Benign	0.018
Sift	Benign	0.73	T
Sift4G	Benign	0.56	T
Polyphen		0.0090	B
Vest4		0.018
MutPred		0.44		Gain of catalytic residue at T177 (P = 0.0581);
MVP		0.24
MPC		0.0029
ClinPred		0.029	T
GERP RS		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.053
gMVP		0.18

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: rs1010709354; hg19: chrX-30237227;