Genetic Variant MAGEA3:p.Ile204Ile (chrX-152701444-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_005362.4(MAGEA3):c.612C>T(p.Ile204Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00471 in 1,208,506 control chromosomes in the GnomAD database, including 180 homozygotes. There are 1,529 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.024 ( 86 hom., 726 hem., cov: 21)

Exomes 𝑓: 0.0027 ( 94 hom. 803 hem. )

Consequence

MAGEA3
NM_005362.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.14

Variant links:

Genes affected

MAGEA3 (HGNC:6801): (MAGE family member A3) 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]

MAGEA3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant X-152701444-C-T is Benign according to our data. Variant chrX-152701444-C-T is described in ClinVar as [Benign]. Clinvar id is 780740.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEA3	NM_005362.4 link	c.612C>T	p.Ile204Ile	synonymous_variant	Exon 3 of 3	ENST00000370278.4	NP_005353.1	P43357

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MAGEA3	ENST00000370278.4 link	c.612C>T	p.Ile204Ile	synonymous_variant	Exon 3 of 3	1	NM_005362.4	ENSP00000359301.3	P43357
MAGEA3	ENST00000598245.2 link	c.612C>T	p.Ile204Ile	synonymous_variant	Exon 3 of 3	2		ENSP00000473093.1	P43357
MAGEA3	ENST00000417212.5 link	c.*17C>T		downstream_gene_variant		2		ENSP00000392758.1	E7EMU0

Frequencies

GnomAD3 genomes

AF:

0.0245

AC:

2735

AN:

111764

Hom.:

Cov.:

AF XY:

0.0214

AC XY:

726

AN XY:

33980

show subpopulations

Gnomad AFR

AF:

0.0840

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0106

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000283

Gnomad SAS

AF:

0.000373

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00424

Gnomad NFE

AF:

0.000264

Gnomad OTH

AF:

0.0212

GnomAD4 exome

AF:

0.00269

AC:

2950

AN:

1096687

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

803

AN XY:

362071

show subpopulations

Gnomad4 AFR exome

AF:

0.0878

Gnomad4 AMR exome

AF:

0.00467

Gnomad4 ASJ exome

AF:

0.0000517

Gnomad4 EAS exome

AF:

0.0000332

Gnomad4 SAS exome

AF:

0.000111

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000176

Gnomad4 OTH exome

AF:

0.00593

GnomAD4 genome

AF:

0.0245

AC:

2739

AN:

111819

Hom.:

Cov.:

AF XY:

0.0213

AC XY:

726

AN XY:

34045

show subpopulations

Gnomad4 AFR

AF:

0.0840

Gnomad4 AMR

AF:

0.0106

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000283

Gnomad4 SAS

AF:

0.000374

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000264

Gnomad4 OTH

AF:

0.0209

Alfa

AF:

0.00905

Hom.:

Bravo

AF:

0.0294

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.82

DANN

Benign

0.59

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