Variant X-30243154-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002367.4(MAGEB4):c.1019G>A(p.Ser340Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000171 in 1,172,300 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 25)

Exomes 𝑓: 9.4e-7 ( 0 hom. 1 hem. )

Consequence

MAGEB4
NM_002367.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.319

Variant links:

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]

MAGEB4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12323794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEB4	NM_002367.4 linkuse as main transcript	c.1019G>A	p.Ser340Asn	missense_variant	1/1	ENST00000378982.4	NP_002358.1	O15481

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEB4	ENST00000378982.4 linkuse as main transcript	c.1019G>A	p.Ser340Asn	missense_variant	1/1	6	NM_002367.4	ENSP00000368266.2		O15481

Frequencies

GnomAD3 genomes

AF:

0.00000889

AC:

AN:

112462

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34614

show subpopulations

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:

0.000374

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000663

AC:

AN:

150809

Hom.:

AF XY:

0.00

AC XY:

AN XY:

48321

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 SAS exome

AF:

0.0000844

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.44e-7

AC:

AN:

1059784

Hom.:

Cov.:

AF XY:

0.00000295

AC XY:

AN XY:

338926

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000213

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000889

AC:

AN:

112516

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34678

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000375

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2023

The c.1019G>A (p.S340N) alteration is located in exon 1 (coding exon 1) of the MAGEB4 gene. This alteration results from a G to A substitution at nucleotide position 1019, causing the serine (S) at amino acid position 340 to be replaced by an asparagine (N). 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

0.15

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.96

CADD

Benign

8.3

DANN

Benign

0.70

DEOGEN2

Benign

0.040

FATHMM_MKL

Benign

0.0078

LIST_S2

Benign

0.19

M_CAP

Benign

0.0028

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.2

REVEL

Benign

0.026

Sift

Benign

0.070

Sift4G

Benign

0.098

Polyphen

0.97

Vest4

0.033

MutPred

0.30

Loss of phosphorylation at S340 (P = 0.005);

MVP

0.11

MPC

0.14

ClinPred

0.076

GERP RS

0.37

Varity_R

0.092

gMVP

0.28

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over