X-30250507-A-G

Variant names:

Variant summary

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

The NM_177404.3(MAGEB1):c.14A>G(p.Gln5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 1,075,045 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000028 ( 0 hom. 0 hem. )

Consequence

MAGEB1
NM_177404.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.33

Publications

0 publications found

Variant links:

Genes affected

MAGEB1 (HGNC:6808): (MAGE family member B1) 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, and expressed in testis and in a significant fraction of tumors of various histological types. This gene and other MAGEB members are clustered on chromosome Xp22-p21. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene, however, the full length nature of some variants has not been defined. [provided by RefSeq, Jul 2008]

MAGEB1 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=0.13414323).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEB1	NM_177404.3 link	c.14A>G	p.Gln5Arg	missense_variant	Exon 2 of 2	ENST00000397548.4	NP_796379.1	P43366
MAGEB1	NM_002363.5 link	c.14A>G	p.Gln5Arg	missense_variant	Exon 4 of 4		NP_002354.2	P43366
MAGEB1	NM_177415.3 link	c.14A>G	p.Gln5Arg	missense_variant	Exon 3 of 3		NP_803134.1	P43366

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAGEB1	ENST00000397548.4 link	c.14A>G	p.Gln5Arg	missense_variant	Exon 2 of 2	1	NM_177404.3	ENSP00000380681.2	P43366
MAGEB1	ENST00000378981.8 link	c.14A>G	p.Gln5Arg	missense_variant	Exon 4 of 4	1		ENSP00000368264.3	P43366
MAGEB1	ENST00000397550.6 link	c.14A>G	p.Gln5Arg	missense_variant	Exon 3 of 3	1		ENSP00000380683.1	P43366

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000279

AC:

AN:

1075045

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

347021

show subpopulations

African (AFR)

AF:

0.0000390

AC:

AN:

25666

American (AMR)

AF:

0.0000310

AC:

AN:

32297

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17938

East Asian (EAS)

AF:

0.00

AC:

AN:

29915

South Asian (SAS)

AF:

0.00

AC:

AN:

49901

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39891

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3966

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

830460

Other (OTH)

AF:

0.0000222

AC:

AN:

45011

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 20, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.14A>G (p.Q5R) alteration is located in exon 4 (coding exon 1) of the MAGEB1 gene. This alteration results from a A to G substitution at nucleotide position 14, causing the glutamine (Q) at amino acid position 5 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

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.091

T;T;T

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.67

.;T;.

M_CAP

Benign

0.0049

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.6

M;M;M

PhyloP100

3.3

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.5

D;D;D

REVEL

Benign

0.091

Sift

Benign

0.038

D;D;D

Sift4G

Uncertain

0.035

D;D;D

Polyphen

0.14

B;B;B

Vest4

0.16

MutPred

0.37

Gain of helix (P = 0.0199);Gain of helix (P = 0.0199);Gain of helix (P = 0.0199);

MVP

0.24

MPC

0.12

ClinPred

0.71

GERP RS

2.8

Varity_R

0.34

gMVP

0.43

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

X-30250507-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over