Variant X-142203969-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_016249.4(MAGEC2):c.19G>A(p.Val7Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,176,011 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 40 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., 3 hem., cov: 22)

Exomes 𝑓: 0.00013 ( 0 hom. 37 hem. )

Consequence

MAGEC2
NM_016249.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:2

Conservation

PhyloP100: -1.48

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.071511626).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEC2	NM_016249.4 linkuse as main transcript	c.19G>A	p.Val7Ile	missense_variant	3/3	ENST00000247452.4	NP_057333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEC2	ENST00000247452.4 linkuse as main transcript	c.19G>A	p.Val7Ile	missense_variant	3/3	1	NM_016249.4	ENSP00000354660	P1
	ENST00000664519.1 linkuse as main transcript	n.300+8185C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000720

AC:

AN:

111187

Hom.:

Cov.:

AF XY:

0.0000898

AC XY:

AN XY:

33413

show subpopulations

Gnomad AFR

AF:

0.0000984

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000945

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000919

AC:

AN:

152326

Hom.:

AF XY:

0.0000617

AC XY:

AN XY:

48646

show subpopulations

Gnomad AFR exome

AF:

0.000157

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000172

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000130

AC:

138

AN:

1064824

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

343190

show subpopulations

Gnomad4 AFR exome

AF:

0.0000395

Gnomad4 AMR exome

AF:

0.0000326

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000208

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000160

Gnomad4 OTH exome

AF:

0.0000673

GnomAD4 genome

AF:

0.0000720

AC:

AN:

111187

Hom.:

Cov.:

AF XY:

0.0000898

AC XY:

AN XY:

33413

show subpopulations

Gnomad4 AFR

AF:

0.0000984

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000945

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000436

Hom.:

Bravo

AF:

0.0000680

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000993

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 13, 2021

The c.19G>A (p.V7I) alteration is located in exon 3 (coding exon 1) of the MAGEC2 gene. This alteration results from a G to A substitution at nucleotide position 19, causing the valine (V) at amino acid position 7 to be replaced by an isoleucine (I). 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

0.076

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.0090

DANN

Benign

0.86

DEOGEN2

Benign

0.023

FATHMM_MKL

Benign

0.0060

LIST_S2

Benign

0.33

M_CAP

Benign

0.0030

MetaRNN

Benign

0.072

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

PrimateAI

Benign

0.39

PROVEAN

Benign

0.10

REVEL

Benign

0.051

Sift

Benign

0.58

Sift4G

Benign

0.51

Polyphen

0.95

Vest4

0.097

MutPred

0.36

Loss of catalytic residue at V7 (P = 0.1756);

MVP

0.043

MPC

0.021

ClinPred

0.019

GERP RS

-1.8

Varity_R

0.056

gMVP

0.072

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