Variant X-152766934-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_005363.5(MAGEA6):c.717C>G(p.Phe239Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00042 in 1,208,878 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 158 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., 5 hem., cov: 21)

Exomes 𝑓: 0.00044 ( 0 hom. 153 hem. )

Consequence

MAGEA6
NM_005363.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.12

Variant links:

Genes affected

MAGEA6 (HGNC:6804): (MAGE family member A6) 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

MAGEA6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10921419).

BP6

Variant X-152766934-G-C is Benign according to our data. Variant chrX-152766934-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2367566.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEA6	NM_005363.5 linkuse as main transcript	c.717C>G	p.Phe239Leu	missense_variant	3/3	ENST00000329342.10	NP_005354.1	P43360
MAGEA6	NM_175868.4 linkuse as main transcript	c.717C>G	p.Phe239Leu	missense_variant	3/3		NP_787064.1	P43360

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAGEA6	ENST00000329342.10 linkuse as main transcript	c.717C>G	p.Phe239Leu	missense_variant	3/3	1	NM_005363.5	ENSP00000329199.5	P43360
MAGEA6	ENST00000616035.4 linkuse as main transcript	c.717C>G	p.Phe239Leu	missense_variant	3/3	5		ENSP00000480637.1	P43360
MAGEA6	ENST00000457643.1 linkuse as main transcript	c.*10C>G		downstream_gene_variant		3		ENSP00000401806.1	E7ETG4

Frequencies

GnomAD3 genomes

AF:

0.000215

AC:

AN:

111679

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

33893

show subpopulations

Gnomad AFR

AF:

0.000196

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:

0.000320

Gnomad OTH

AF:

0.000668

GnomAD4 exome

AF:

0.000441

AC:

484

AN:

1097145

Hom.:

Cov.:

AF XY:

0.000422

AC XY:

153

AN XY:

362555

show subpopulations

Gnomad4 AFR exome

AF:

0.000189

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000994

Gnomad4 SAS exome

AF:

0.0000370

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000552

Gnomad4 OTH exome

AF:

0.000174

GnomAD4 genome

AF:

0.000215

AC:

AN:

111733

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

AN XY:

33957

show subpopulations

Gnomad4 AFR

AF:

0.000195

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:

0.000320

Gnomad4 OTH

AF:

0.000659

Alfa

AF:

0.000255

Hom.:

Bravo

AF:

0.000257

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

CADD

Benign

0.0040

DEOGEN2

Benign

0.036

T;T

LIST_S2

Benign

0.30

.;T

MetaRNN

Benign

0.11

T;T

PROVEAN

Pathogenic

-4.4

D;.

Sift

Benign

0.090

T;.

Sift4G

Uncertain

0.048

D;D

Vest4

0.023

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.52

Splicing

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