Variant X-141881494-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_138702.1(MAGEC3):c.607G>A(p.Glu203Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000293 in 1,209,644 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 105 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., 4 hem., cov: 22)

Exomes 𝑓: 0.00030 ( 0 hom. 101 hem. )

Consequence

MAGEC3
NM_138702.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.802

Variant links:

Genes affected

MAGEC3 (HGNC:23798): (MAGE family member C3) This gene is a member of the MAGEC gene family. The members of this family are not expressed in normal tissues, except for testis, and are expressed in tumors of various histological types. The MAGEC genes are clustered on chromosome Xq26-q27. Two transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MAGEC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03518212).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEC3	NM_138702.1 link	c.607G>A	p.Glu203Lys	missense_variant	4/8	ENST00000298296.1	NP_619647.1	Q8TD91-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEC3	ENST00000298296.1 link	c.607G>A	p.Glu203Lys	missense_variant	4/8	1	NM_138702.1	ENSP00000298296.1		Q8TD91-1
MAGEC3	ENST00000443323.2 link	c.-119+891G>A		intron_variant		1		ENSP00000438254.1		Q3SYA6

Frequencies

GnomAD3 genomes

AF:

0.000224

AC:

AN:

111766

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33940

show subpopulations

Gnomad AFR

AF:

0.0000326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000946

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000375

Gnomad FIN

AF:

0.000165

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000395

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000366

AC:

AN:

182986

Hom.:

AF XY:

0.000371

AC XY:

AN XY:

67468

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.000268

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000737

Gnomad FIN exome

AF:

0.000125

Gnomad NFE exome

AF:

0.000551

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.000300

AC:

329

AN:

1097878

Hom.:

Cov.:

AF XY:

0.000278

AC XY:

101

AN XY:

363254

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.000103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000573

Gnomad4 FIN exome

AF:

0.000148

Gnomad4 NFE exome

AF:

0.000320

Gnomad4 OTH exome

AF:

0.000369

GnomAD4 genome

AF:

0.000224

AC:

AN:

111766

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33940

show subpopulations

Gnomad4 AFR

AF:

0.0000326

Gnomad4 AMR

AF:

0.0000946

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000375

Gnomad4 FIN

AF:

0.000165

Gnomad4 NFE

AF:

0.000395

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000618

Hom.:

Bravo

AF:

0.000242

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000379

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

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 02, 2021

The c.607G>A (p.E203K) alteration is located in exon 4 (coding exon 4) of the MAGEC3 gene. This alteration results from a G to A substitution at nucleotide position 607, causing the glutamic acid (E) at amino acid position 203 to be replaced by a lysine (K). 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

0.19

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.97

CADD

Benign

8.5

DANN

Benign

0.90

DEOGEN2

Benign

0.0077

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.84

M_CAP

Benign

0.033

MetaRNN

Benign

0.035

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.18

REVEL

Benign

0.045

Sift

Benign

0.038

Sift4G

Uncertain

0.021

Polyphen

0.74

Vest4

0.026

MVP

0.014

MPC

0.084

ClinPred

0.0074

GERP RS

-0.90

Varity_R

0.050

gMVP

0.23

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