X-149884891-A-G

Position:

chrX-149884891-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_005364.5(MAGEA8):c.619A>G(p.Ile207Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,097,934 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. 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 (no stars).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 2 hem. )

Consequence

MAGEA8
NM_005364.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: -2.12

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05328533).

BP6

Variant X-149884891-A-G is Benign according to our data. Variant chrX-149884891-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1206170.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-149884891-A-G is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAGEA8	NM_005364.5 linkuse as main transcript	c.619A>G	p.Ile207Val	missense_variant	3/3	ENST00000286482.6	NP_005355.2
MAGEA8-AS1	NR_102703.1 linkuse as main transcript	n.81-2393T>C		intron_variant, non_coding_transcript_variant
MAGEA8	NM_001166400.2 linkuse as main transcript	c.619A>G	p.Ile207Val	missense_variant	4/4		NP_001159872.1
MAGEA8	NM_001166401.2 linkuse as main transcript	c.619A>G	p.Ile207Val	missense_variant	3/3		NP_001159873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MAGEA8	ENST00000286482.6 linkuse as main transcript	c.619A>G	p.Ile207Val	missense_variant	3/3	1	NM_005364.5	ENSP00000286482	P1
MAGEA8	ENST00000535454.5 linkuse as main transcript	c.619A>G	p.Ile207Val	missense_variant	4/4	3		ENSP00000438293	P1
MAGEA8	ENST00000542674.5 linkuse as main transcript	c.619A>G	p.Ile207Val	missense_variant	3/3	3		ENSP00000443776	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

182886

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

67330

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000182

AC:

AN:

1097934

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

363290

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.30

DANN

Benign

0.77

DEOGEN2

Benign

0.0055

T;T;T

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.38

.;T;.

M_CAP

Benign

0.00097

MetaRNN

Benign

0.053

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.0

L;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.81

N;N;N

REVEL

Benign

0.016

Sift

Benign

0.080

T;T;T

Sift4G

Benign

0.21

T;T;T

Polyphen

0.029

B;B;B

Vest4

0.025

MVP

0.22

MPC

0.19

ClinPred

0.035

GERP RS

-0.76

Varity_R

0.11

gMVP

0.20

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