Variant X-142203247-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The ENST00000247452.4(MAGEC2):c.741G>C(p.Glu247Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000579 in 1,209,288 control chromosomes in the GnomAD database, including 1 homozygotes. There are 2 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 0.000054 ( 1 hom., 2 hem., cov: 22)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

MAGEC2
ENST00000247452.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.108

Variant links:

Genes affected

MAGEC2 (HGNC:13574): (MAGE family member C2) This gene is a member of the MAGEC gene family. It is not expressed in normal tissues, except for testis, and is expressed in tumors of various histological types. This gene and the other MAGEC genes are clustered on chromosome Xq26-q27. [provided by RefSeq, Oct 2009]

MAGEC2 links:

ENSG00000288098 (HGNC:):

ENSG00000288098 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.33107617).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEC2	NM_016249.4 linkuse as main transcript	c.741G>C	p.Glu247Asp	missense_variant	3/3	ENST00000247452.4	NP_057333.1	Q9UBF1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEC2	ENST00000247452.4 linkuse as main transcript	c.741G>C	p.Glu247Asp	missense_variant	3/3	1	NM_016249.4	ENSP00000354660.2		Q9UBF1
ENSG00000288098	ENST00000664519.1 linkuse as main transcript	n.300+7463C>G		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0000540

AC:

AN:

111039

Hom.:

Cov.:

AF XY:

0.0000602

AC XY:

AN XY:

33235

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000952

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:

0.0000378

Gnomad OTH

AF:

0.00200

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1098249

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363603

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000540

AC:

AN:

111039

Hom.:

Cov.:

AF XY:

0.0000602

AC XY:

AN XY:

33235

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000952

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000378

Gnomad4 OTH

AF:

0.00200

Bravo

AF:

0.0000453

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

Apr 23, 2024

The c.741G>C (p.E247D) alteration is located in exon 3 (coding exon 1) of the MAGEC2 gene. This alteration results from a G to C substitution at nucleotide position 741, causing the glutamic acid (E) at amino acid position 247 to be replaced by an aspartic acid (D). 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

0.15

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.85

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.62

M_CAP

Benign

0.0032

MetaRNN

Benign

0.33

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.037

Sift

Benign

0.036

Sift4G

Uncertain

0.060

Polyphen

0.95

Vest4

0.14

MutPred

0.70

Loss of helix (P = 0.4763);

MVP

0.093

MPC

0.030

ClinPred

0.88

GERP RS

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.30

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