Genetic Variant MAGEB2:p.Thr67Ile (chrX-30218780-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002364.5(MAGEB2):c.200C>T(p.Thr67Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000371 in 1,077,635 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T67S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000037 ( 0 hom. 1 hem. )

Consequence

MAGEB2
NM_002364.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.281

Publications

0 publications found

Variant links:

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]

MAGEB2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11910328).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002364.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEB2	NM_002364.5	MANE Select	c.200C>T	p.Thr67Ile	missense	Exon 2 of 2	NP_002355.2	O15479

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEB2	ENST00000378988.5	TSL:1 MANE Select	c.200C>T	p.Thr67Ile	missense	Exon 2 of 2	ENSP00000368273.4	O15479

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000698

AC:

AN:

143250

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000169

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000371

AC:

AN:

1077635

Hom.:

Cov.:

AF XY:

0.00000285

AC XY:

AN XY:

350553

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25853

American (AMR)

AF:

0.00

AC:

AN:

31736

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19076

East Asian (EAS)

AF:

0.00

AC:

AN:

29305

South Asian (SAS)

AF:

0.00

AC:

AN:

51835

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39185

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4094

European-Non Finnish (NFE)

AF:

0.00000481

AC:

AN:

831195

Other (OTH)

AF:

0.00

AC:

AN:

45356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-1.0

CADD

Benign

6.6

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.015

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.21

M_CAP

Benign

0.0024

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.3

PhyloP100

-0.28

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.9

REVEL

Benign

0.042

Sift

Benign

0.049

Sift4G

Uncertain

0.050

Polyphen

0.83

Vest4

0.079

MutPred

0.28

Loss of glycosylation at T67 (P = 0.002)

MVP

0.19

MPC

0.0028

ClinPred

0.11

GERP RS

-1.8

Varity_R

0.073

gMVP

0.12

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over