Variant X-152766838-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005363.5(MAGEA6):c.813C>G(p.Phe271Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000448 in 1,209,156 control chromosomes in the GnomAD database, including 4 homozygotes. There are 169 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., 6 hem., cov: 21)

Exomes 𝑓: 0.00046 ( 4 hom. 163 hem. )

Consequence

MAGEA6
NM_005363.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.706

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 -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEA6	NM_005363.5 linkuse as main transcript	c.813C>G	p.Phe271Leu	missense_variant	3/3	ENST00000329342.10	NP_005354.1	P43360
MAGEA6	NM_175868.4 linkuse as main transcript	c.813C>G	p.Phe271Leu	missense_variant	3/3		NP_787064.1	P43360

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEA6	ENST00000329342.10 linkuse as main transcript	c.813C>G	p.Phe271Leu	missense_variant	3/3	1	NM_005363.5	ENSP00000329199.5		P43360
MAGEA6	ENST00000616035.4 linkuse as main transcript	c.813C>G	p.Phe271Leu	missense_variant	3/3	5		ENSP00000480637.1		P43360

Frequencies

GnomAD3 genomes

AF:

0.000286

AC:

AN:

111837

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

AN XY:

34027

show subpopulations

Gnomad AFR

AF:

0.0000977

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000472

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:

0.000452

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000465

AC:

510

AN:

1097266

Hom.:

Cov.:

AF XY:

0.000449

AC XY:

163

AN XY:

362626

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.000171

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000663

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.000575

Gnomad4 OTH exome

AF:

0.000347

GnomAD4 genome

AF:

0.000286

AC:

AN:

111890

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

AN XY:

34090

show subpopulations

Gnomad4 AFR

AF:

0.0000975

Gnomad4 AMR

AF:

0.000471

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000452

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000216

Hom.:

Bravo

AF:

0.000423

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

Oct 31, 2023

The c.813C>G (p.F271L) 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 813, causing the phenylalanine (F) at amino acid position 271 to be replaced by a leucine (L). 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

Pathogenic

0.93

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

T;T

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.82

.;T

M_CAP

Benign

0.00072

MetaRNN

Uncertain

0.72

D;D

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-5.5

D;.

Sift

Uncertain

0.016

D;.

Sift4G

Uncertain

0.026

D;D

Vest4

0.24

MutPred

0.95

Loss of sheet (P = 0.1501);Loss of sheet (P = 0.1501);

MVP

0.50

ClinPred

1.0

GERP RS

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.68

gMVP

0.69

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