Variant X-153183162-A-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 ENST00000356661.7(MAGEA1):c.773A>C(p.Asp258Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,210,898 control chromosomes in the GnomAD database, including 2 homozygotes. There are 463 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 0.00079 ( 0 hom., 20 hem., cov: 23)

Exomes 𝑓: 0.0012 ( 2 hom. 443 hem. )

Consequence

MAGEA1
ENST00000356661.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.955

Variant links:

Genes affected

MAGEA1 (HGNC:6796): (MAGE family member A1) 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. [provided by RefSeq, Jul 2008]

MAGEA1 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=0.1992214).

BS2

High Hemizygotes in GnomAd4 at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEA1	NM_004988.5 linkuse as main transcript	c.773A>C	p.Asp258Ala	missense_variant	3/3	ENST00000356661.7	NP_004979.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEA1	ENST00000356661.7 linkuse as main transcript	c.773A>C	p.Asp258Ala	missense_variant	3/3	1	NM_004988.5	ENSP00000349085	P1

Frequencies

GnomAD3 genomes

AF:

0.000790

AC:

AN:

112662

Hom.:

Cov.:

AF XY:

0.000575

AC XY:

AN XY:

34796

show subpopulations

Gnomad AFR

AF:

0.000355

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000558

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000366

Gnomad FIN

AF:

0.000161

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00129

Gnomad OTH

AF:

0.000660

GnomAD3 exomes

AF:

0.000681

AC:

125

AN:

183491

Hom.:

AF XY:

0.000883

AC XY:

AN XY:

67921

show subpopulations

Gnomad AFR exome

AF:

0.000380

Gnomad AMR exome

AF:

0.000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000786

Gnomad FIN exome

AF:

0.0000625

Gnomad NFE exome

AF:

0.00113

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.00121

AC:

1326

AN:

1098236

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

443

AN XY:

363590

show subpopulations

Gnomad4 AFR exome

AF:

0.000227

Gnomad4 AMR exome

AF:

0.000398

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000609

Gnomad4 FIN exome

AF:

0.0000493

Gnomad4 NFE exome

AF:

0.00147

Gnomad4 OTH exome

AF:

0.000651

GnomAD4 genome

AF:

0.000790

AC:

AN:

112662

Hom.:

Cov.:

AF XY:

0.000575

AC XY:

AN XY:

34796

show subpopulations

Gnomad4 AFR

AF:

0.000355

Gnomad4 AMR

AF:

0.000558

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000366

Gnomad4 FIN

AF:

0.000161

Gnomad4 NFE

AF:

0.00129

Gnomad4 OTH

AF:

0.000660

Alfa

AF:

0.000651

Hom.:

Bravo

AF:

0.000688

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

Aug 12, 2021

The c.773A>C (p.D258A) alteration is located in exon 3 (coding exon 1) of the MAGEA1 gene. This alteration results from a A to C substitution at nucleotide position 773, causing the aspartic acid (D) at amino acid position 258 to be replaced by an alanine (A). 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

0.26

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.18

LIST_S2

Benign

0.31

MetaRNN

Benign

0.20

PROVEAN

Pathogenic

-7.4

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Vest4

0.25

gMVP

0.90

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