Genetic Variant MAGEA3:p.Glu115Lys (chrX-152701175-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_005362.4(MAGEA3):c.343G>A(p.Glu115Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., 7 hem., cov: 21)

Exomes 𝑓: 0.00075 ( 6 hom. 446 hem. )

Failed GnomAD Quality Control

Consequence

MAGEA3
NM_005362.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.509

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1510337).

BP6

Variant X-152701175-G-A is Benign according to our data. Variant chrX-152701175-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 726564.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-152701175-G-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEA3	NM_005362.4 link	c.343G>A	p.Glu115Lys	missense_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.343G>A	p.Glu115Lys	missense_variant	Exon 3 of 3	1	NM_005362.4	ENSP00000359301.3	P43357
MAGEA3	ENST00000598245.2 link	c.343G>A	p.Glu115Lys	missense_variant	Exon 3 of 3	2		ENSP00000473093.1	P43357
MAGEA3	ENST00000417212.5 link	c.343G>A	p.Glu115Lys	missense_variant	Exon 3 of 3	2		ENSP00000392758.1	E7EMU0

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

110334

Hom.:

Cov.:

AF XY:

0.000213

AC XY:

AN XY:

32924

FAILED QC

Gnomad AFR

AF:

0.000329

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000285

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00377

Gnomad SAS

AF:

0.00353

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.00135

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000750

AC:

821

AN:

1094811

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

446

AN XY:

361223

show subpopulations

Gnomad4 AFR exome

AF:

0.000228

Gnomad4 AMR exome

AF:

0.000228

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00588

Gnomad4 SAS exome

AF:

0.00243

Gnomad4 FIN exome

AF:

0.000149

Gnomad4 NFE exome

AF:

0.000535

Gnomad4 OTH exome

AF:

0.000849

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000580

AC:

AN:

110390

Hom.:

Cov.:

AF XY:

0.000212

AC XY:

AN XY:

32990

show subpopulations

Gnomad4 AFR

AF:

0.000328

Gnomad4 AMR

AF:

0.000285

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00378

Gnomad4 SAS

AF:

0.00354

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.00133

Alfa

AF:

0.00138

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 22, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

CADD

Benign

7.5

DEOGEN2

Benign

0.34

T;T;T

LIST_S2

Benign

0.065

.;T;T

MetaRNN

Benign

0.15

T;T;T

PROVEAN

Uncertain

-2.6

D;D;.

Sift

Benign

0.66

T;D;.

Sift4G

Benign

0.20

T;D;T

Vest4

0.19

gMVP

0.41

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