Variant X-152767101-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005363.5(MAGEA6):c.550C>G(p.Leu184Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000091 in 1,209,051 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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 0.0000089 ( 0 hom., 0 hem., cov: 21)

Exomes 𝑓: 0.0000091 ( 0 hom. 3 hem. )

Consequence

MAGEA6
NM_005363.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.159

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16818675).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEA6	NM_005363.5 linkuse as main transcript	c.550C>G	p.Leu184Val	missense_variant	3/3	ENST00000329342.10	NP_005354.1	P43360
MAGEA6	NM_175868.4 linkuse as main transcript	c.550C>G	p.Leu184Val	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.550C>G	p.Leu184Val	missense_variant	3/3	1	NM_005363.5	ENSP00000329199.5	P43360
MAGEA6	ENST00000616035.4 linkuse as main transcript	c.550C>G	p.Leu184Val	missense_variant	3/3	5		ENSP00000480637.1	P43360
MAGEA6	ENST00000457643.1 linkuse as main transcript	c.550C>G	p.Leu184Val	missense_variant	4/4	3		ENSP00000401806.1	E7ETG4
MAGEA6	ENST00000412733.1 linkuse as main transcript	c.550C>G	p.Leu184Val	missense_variant	3/3	5		ENSP00000403303.1	E7EUF2

Frequencies

GnomAD3 genomes

AF:

0.00000895

AC:

AN:

111772

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33958

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000546

AC:

AN:

183114

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67552

show subpopulations

Gnomad AFR exome

AF:

0.0000761

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000911

AC:

AN:

1097279

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

362639

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:

0.00000357

Gnomad4 OTH exome

AF:

0.0000868

GnomAD4 genome

AF:

0.00000895

AC:

AN:

111772

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33958

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000825

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 28, 2023

The c.550C>G (p.L184V) alteration is located in exon 3 (coding exon 1) of the MAGEA6 gene. This alteration results from a C to G substitution at nucleotide position 550, causing the leucine (L) at amino acid position 184 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

Benign

0.28

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;T;.;T

FATHMM_MKL

Benign

0.021

LIST_S2

Uncertain

0.87

.;D;D;D

M_CAP

Benign

0.00043

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.9

D;.;D;D

Sift

Uncertain

0.010

D;.;D;D

Sift4G

Uncertain

0.0050

D;D;.;.

Vest4

0.061

MVP

0.48

ClinPred

0.41

GERP RS

0.32

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.24

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