Variant X-141906113-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_005462.5(MAGEC1):c.709G>A(p.Val237Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000454 in 88,029 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.00029 ( 6 hom. 47 hem. )

Failed GnomAD Quality Control

Consequence

MAGEC1
NM_005462.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.432

Variant links:

Genes affected

MAGEC1 (HGNC:6812): (MAGE family member C1) This gene is a member of the melanoma antigen gene (MAGE) family. The proteins of this family are tumor-specific antigens that can be recognized by autologous cytolytic T lymphocytes. This protein contains a large number of unique short repetitive sequences in front of the MAGE-homologous sequence, and therefore is about 800 aa longer than the other MAGE proteins. [provided by RefSeq, Jul 2008]

MAGEC1 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=0.02742052).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEC1	NM_005462.5 linkuse as main transcript	c.709G>A	p.Val237Met	missense_variant	4/4	ENST00000285879.5	NP_005453.2
MAGEC1	XM_011531418.3 linkuse as main transcript	c.709G>A	p.Val237Met	missense_variant	4/4		XP_011529720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEC1	ENST00000285879.5 linkuse as main transcript	c.709G>A	p.Val237Met	missense_variant	4/4	1	NM_005462.5	ENSP00000285879	P3	O60732-1
MAGEC1	ENST00000406005.2 linkuse as main transcript	c.-115+566G>A		intron_variant		1		ENSP00000385500	A2	O60732-2

Frequencies

GnomAD3 genomes

AF:

0.000455

AC:

AN:

87976

Hom.:

Cov.:

AF XY:

0.0000803

AC XY:

AN XY:

24904

show subpopulations

Gnomad AFR

AF:

0.000630

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000570

Gnomad ASJ

AF:

0.000941

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000522

Gnomad FIN

AF:

0.000221

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000346

Gnomad OTH

AF:

0.000830

GnomAD3 exomes

AF:

0.000168

AC:

AN:

172295

Hom.:

AF XY:

0.0000665

AC XY:

AN XY:

60177

show subpopulations

Gnomad AFR exome

AF:

0.000963

Gnomad AMR exome

AF:

0.0000377

Gnomad ASJ exome

AF:

0.000725

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000574

Gnomad FIN exome

AF:

0.0000660

Gnomad NFE exome

AF:

0.000118

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000289

AC:

214

AN:

740243

Hom.:

Cov.:

AF XY:

0.000221

AC XY:

AN XY:

212477

show subpopulations

Gnomad4 AFR exome

AF:

0.00167

Gnomad4 AMR exome

AF:

0.000497

Gnomad4 ASJ exome

AF:

0.000626

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000238

Gnomad4 FIN exome

AF:

0.0000293

Gnomad4 NFE exome

AF:

0.000248

Gnomad4 OTH exome

AF:

0.000295

GnomAD4 genome

AF:

0.000454

AC:

AN:

88029

Hom.:

Cov.:

AF XY:

0.0000801

AC XY:

AN XY:

24959

show subpopulations

Gnomad4 AFR

AF:

0.000628

Gnomad4 AMR

AF:

0.000570

Gnomad4 ASJ

AF:

0.000941

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000525

Gnomad4 FIN

AF:

0.000221

Gnomad4 NFE

AF:

0.000346

Gnomad4 OTH

AF:

0.000818

Alfa

AF:

0.000927

Hom.:

ExAC

AF:

0.000562

AC:

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

Sep 16, 2021

The c.709G>A (p.V237M) alteration is located in exon 4 (coding exon 2) of the MAGEC1 gene. This alteration results from a G to A substitution at nucleotide position 709, causing the valine (V) at amino acid position 237 to be replaced by a methionine (M). 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

Uncertain

0.44

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.0060

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.35

M_CAP

Benign

0.0017

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.13

REVEL

Benign

0.059

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.031

Polyphen

0.31

Vest4

0.058

MVP

0.067

ClinPred

0.018

Varity_R

0.083

gMVP

0.013

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