Variant X-149884684-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005364.5(MAGEA8):c.412A>G(p.Met138Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Consequence

MAGEA8
NM_005364.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.405

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MAGEA8	NM_005364.5 linkuse as main transcript	c.412A>G	p.Met138Val	missense_variant	3/3	ENST00000286482.6	NP_005355.2
MAGEA8-AS1	NR_102703.1 linkuse as main transcript	n.81-2186T>C		intron_variant, non_coding_transcript_variant
MAGEA8	NM_001166400.2 linkuse as main transcript	c.412A>G	p.Met138Val	missense_variant	4/4		NP_001159872.1
MAGEA8	NM_001166401.2 linkuse as main transcript	c.412A>G	p.Met138Val	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.412A>G	p.Met138Val	missense_variant	3/3	1	NM_005364.5	ENSP00000286482	P1
MAGEA8	ENST00000535454.5 linkuse as main transcript	c.412A>G	p.Met138Val	missense_variant	4/4	3		ENSP00000438293	P1
MAGEA8	ENST00000542674.5 linkuse as main transcript	c.412A>G	p.Met138Val	missense_variant	3/3	3		ENSP00000443776	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

Jan 07, 2022

The c.412A>G (p.M138V) alteration is located in exon 4 (coding exon 1) of the MAGEA8 gene. This alteration results from a A to G substitution at nucleotide position 412, causing the methionine (M) at amino acid position 138 to be replaced by a valine (V). 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

Uncertain

0.39

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.11

T;T;T

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.78

.;T;.

M_CAP

Benign

0.0010

MetaRNN

Uncertain

0.56

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

M;M;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Benign

0.069

Sift

Uncertain

0.0020

D;D;D

Sift4G

Benign

0.082

T;T;T

Polyphen

0.93

P;P;P

Vest4

0.41

MutPred

0.80

Gain of ubiquitination at K135 (P = 0.064);Gain of ubiquitination at K135 (P = 0.064);Gain of ubiquitination at K135 (P = 0.064);

MVP

0.29

MPC

0.37

ClinPred

0.83

GERP RS

0.96

Varity_R

0.64

gMVP

0.41

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over