Variant X-141905856-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005462.5(MAGEC1):c.452C>T(p.Thr151Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,197,229 control chromosomes in the GnomAD database, including 77,725 homozygotes. There are 165,329 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.37 ( 5747 hom., 11523 hem., cov: 23)

Exomes 𝑓: 0.43 ( 71978 hom. 153806 hem. )

Consequence

MAGEC1
NM_005462.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.627

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012508154).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEC1	NM_005462.5 linkuse as main transcript	c.452C>T	p.Thr151Ile	missense_variant	4/4	ENST00000285879.5	NP_005453.2	O60732-1
MAGEC1	XM_011531418.3 linkuse as main transcript	c.452C>T	p.Thr151Ile	missense_variant	4/4		XP_011529720.1	O60732-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEC1	ENST00000285879.5 linkuse as main transcript	c.452C>T	p.Thr151Ile	missense_variant	4/4	1	NM_005462.5	ENSP00000285879.4		O60732-1
MAGEC1	ENST00000406005.2 linkuse as main transcript	c.-115+309C>T		intron_variant		1		ENSP00000385500.2		O60732-2

Frequencies

GnomAD3 genomes

AF:

0.367

AC:

40307

AN:

109915

Hom.:

5751

Cov.:

AF XY:

0.352

AC XY:

11525

AN XY:

32751

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.265

Gnomad AMR

AF:

0.328

Gnomad ASJ

AF:

0.396

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.246

Gnomad FIN

AF:

0.406

Gnomad MID

AF:

0.369

Gnomad NFE

AF:

0.457

Gnomad OTH

AF:

0.335

GnomAD3 exomes

AF:

0.379

AC:

61196

AN:

161287

Hom.:

7725

AF XY:

0.400

AC XY:

24018

AN XY:

60011

show subpopulations

Gnomad AFR exome

AF:

0.238

Gnomad AMR exome

AF:

0.301

Gnomad ASJ exome

AF:

0.411

Gnomad EAS exome

AF:

0.171

Gnomad SAS exome

AF:

0.252

Gnomad FIN exome

AF:

0.457

Gnomad NFE exome

AF:

0.475

Gnomad OTH exome

AF:

0.398

GnomAD4 exome

AF:

0.433

AC:

470724

AN:

1087261

Hom.:

71978

Cov.:

AF XY:

0.426

AC XY:

153806

AN XY:

361399

show subpopulations

Gnomad4 AFR exome

AF:

0.238

Gnomad4 AMR exome

AF:

0.311

Gnomad4 ASJ exome

AF:

0.409

Gnomad4 EAS exome

AF:

0.191

Gnomad4 SAS exome

AF:

0.254

Gnomad4 FIN exome

AF:

0.425

Gnomad4 NFE exome

AF:

0.467

Gnomad4 OTH exome

AF:

0.404

GnomAD4 genome

AF:

0.366

AC:

40292

AN:

109968

Hom.:

5747

Cov.:

AF XY:

0.351

AC XY:

11523

AN XY:

32812

show subpopulations

Gnomad4 AFR

AF:

0.248

Gnomad4 AMR

AF:

0.327

Gnomad4 ASJ

AF:

0.396

Gnomad4 EAS

AF:

0.187

Gnomad4 SAS

AF:

0.244

Gnomad4 FIN

AF:

0.406

Gnomad4 NFE

AF:

0.457

Gnomad4 OTH

AF:

0.333

Alfa

AF:

0.114

Hom.:

367

Bravo

AF:

0.359

TwinsUK

AF:

0.465

AC:

1724

ALSPAC

AF:

0.468

AC:

1351

ESP6500AA

AF:

0.260

AC:

997

ESP6500EA

AF:

0.453

AC:

3046

ExAC

AF:

0.371

AC:

44694

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.97

BayesDel_noAF

Benign

-1.0

CADD

Benign

4.4

DANN

Benign

0.27

DEOGEN2

Benign

0.0030

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.33

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.72

REVEL

Benign

0.066

Sift

Benign

0.43

Sift4G

Uncertain

0.021

Polyphen

0.90

Vest4

0.025

ClinPred

0.010

Varity_R

0.050

gMVP

0.027

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over