Variant X-149884309-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005364.5(MAGEA8):c.37G>A(p.Glu13Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,203,179 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 36 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., 19 hem., cov: 24)

Exomes 𝑓: 0.000069 ( 0 hom. 17 hem. )

Consequence

MAGEA8
NM_005364.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0420

Variant links:

Genes affected

MAGEA8 (HGNC:6806): (MAGE family member A8) This gene is a member of the MAGEA gene family. The members of this family encode proteins with 50 to 80% sequence identity to each other. The promoters and first exons of the MAGEA genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. The MAGEA genes are clustered at chromosomal location Xq28. They have been implicated in some hereditary disorders, such as dyskeratosis congenita. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Oct 2009]

MAGEA8 links:

MAGEA8-AS1 (HGNC:):

MAGEA8-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012631774).

BS2

High Hemizygotes in GnomAd4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAGEA8	NM_005364.5 linkuse as main transcript	c.37G>A	p.Glu13Lys	missense_variant	3/3	ENST00000286482.6	NP_005355.2
MAGEA8-AS1	NR_102703.1 linkuse as main transcript	n.81-1811C>T		intron_variant, non_coding_transcript_variant
MAGEA8	NM_001166400.2 linkuse as main transcript	c.37G>A	p.Glu13Lys	missense_variant	4/4		NP_001159872.1
MAGEA8	NM_001166401.2 linkuse as main transcript	c.37G>A	p.Glu13Lys	missense_variant	3/3		NP_001159873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEA8	ENST00000286482.6 linkuse as main transcript	c.37G>A	p.Glu13Lys	missense_variant	3/3	1	NM_005364.5	ENSP00000286482	P1

Frequencies

GnomAD3 genomes

AF:

0.000542

AC:

AN:

112603

Hom.:

Cov.:

AF XY:

0.000547

AC XY:

AN XY:

34743

show subpopulations

Gnomad AFR

AF:

0.00197

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000227

AC:

AN:

167456

Hom.:

AF XY:

0.0000936

AC XY:

AN XY:

53400

show subpopulations

Gnomad AFR exome

AF:

0.00268

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000134

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000688

AC:

AN:

1090520

Hom.:

Cov.:

AF XY:

0.0000476

AC XY:

AN XY:

357118

show subpopulations

Gnomad4 AFR exome

AF:

0.00240

Gnomad4 AMR exome

AF:

0.000174

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000239

Gnomad4 OTH exome

AF:

0.0000874

GnomAD4 genome

AF:

0.000541

AC:

AN:

112659

Hom.:

Cov.:

AF XY:

0.000546

AC XY:

AN XY:

34807

show subpopulations

Gnomad4 AFR

AF:

0.00196

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000555

Hom.:

Bravo

AF:

0.000812

ESP6500AA

AF:

0.00183

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000222

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

Sep 29, 2023

The c.37G>A (p.E13K) alteration is located in exon 4 (coding exon 1) of the MAGEA8 gene. This alteration results from a G to A substitution at nucleotide position 37, causing the glutamic acid (E) at amino acid position 13 to be replaced by a lysine (K). 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

-0.81

BayesDel_noAF

Benign

-0.94

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

T;T;T

FATHMM_MKL

Benign

0.0053

LIST_S2

Benign

0.70

.;T;.

M_CAP

Benign

0.00066

MetaRNN

Benign

0.013

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;M;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Benign

0.032

Sift

Uncertain

0.022

D;D;D

Sift4G

Uncertain

0.049

D;D;D

Polyphen

0.98

D;D;D

Vest4

0.096

MVP

0.31

MPC

0.41

ClinPred

0.054

GERP RS

0.99

Varity_R

0.35

gMVP

0.30

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