Variant rs176036 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.74G>A(p.Cys25Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,209,037 control chromosomes in the GnomAD database, including 18,094 homozygotes. There are 77,651 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. 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 0.18 ( 1386 hom., 5551 hem., cov: 23)

Exomes 𝑓: 0.20 ( 16708 hom. 72100 hem. )

Consequence

MAGEC1
NM_005462.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.29

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=0.0052823722).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 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.74G>A	p.Cys25Tyr	missense_variant	4/4	ENST00000285879.5	NP_005453.2	O60732-1
MAGEC1	XM_011531418.3 linkuse as main transcript	c.74G>A	p.Cys25Tyr	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.74G>A	p.Cys25Tyr	missense_variant	4/4	1	NM_005462.5	ENSP00000285879.4		O60732-1
MAGEC1	ENST00000406005 linkuse as main transcript	c.-184G>A		5_prime_UTR_variant	3/4	1		ENSP00000385500.2		O60732-2

Frequencies

GnomAD3 genomes

AF:

0.179

AC:

19926

AN:

111577

Hom.:

1388

Cov.:

AF XY:

0.164

AC XY:

5551

AN XY:

33817

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.0642

Gnomad SAS

AF:

0.0514

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.216

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.167

GnomAD3 exomes

AF:

0.177

AC:

32328

AN:

183042

Hom.:

1984

AF XY:

0.171

AC XY:

11542

AN XY:

67558

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.198

Gnomad ASJ exome

AF:

0.201

Gnomad EAS exome

AF:

0.0652

Gnomad SAS exome

AF:

0.0585

Gnomad FIN exome

AF:

0.179

Gnomad NFE exome

AF:

0.216

Gnomad OTH exome

AF:

0.187

GnomAD4 exome

AF:

0.205

AC:

224711

AN:

1097406

Hom.:

16708

Cov.:

AF XY:

0.199

AC XY:

72100

AN XY:

362846

show subpopulations

Gnomad4 AFR exome

AF:

0.145

Gnomad4 AMR exome

AF:

0.195

Gnomad4 ASJ exome

AF:

0.196

Gnomad4 EAS exome

AF:

0.0720

Gnomad4 SAS exome

AF:

0.0637

Gnomad4 FIN exome

AF:

0.182

Gnomad4 NFE exome

AF:

0.223

Gnomad4 OTH exome

AF:

0.189

GnomAD4 genome

AF:

0.178

AC:

19919

AN:

111631

Hom.:

1386

Cov.:

AF XY:

0.164

AC XY:

5551

AN XY:

33881

show subpopulations

Gnomad4 AFR

AF:

0.151

Gnomad4 AMR

AF:

0.169

Gnomad4 ASJ

AF:

0.184

Gnomad4 EAS

AF:

0.0644

Gnomad4 SAS

AF:

0.0504

Gnomad4 FIN

AF:

0.169

Gnomad4 NFE

AF:

0.212

Gnomad4 OTH

AF:

0.167

Alfa

AF:

0.194

Hom.:

10467

Bravo

AF:

0.181

TwinsUK

AF:

0.214

AC:

793

ALSPAC

AF:

0.216

AC:

625

ESP6500AA

AF:

0.160

AC:

612

ESP6500EA

AF:

0.208

AC:

1399

ExAC

AF:

0.173

AC:

21001

EpiCase

AF:

0.214

EpiControl

AF:

0.209

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.88

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.0

DANN

Benign

0.65

DEOGEN2

Benign

0.0030

FATHMM_MKL

Benign

0.0070

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0053

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.34

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.10

REVEL

Benign

0.095

Sift

Benign

0.15

Sift4G

Benign

1.0

Polyphen

0.80

Vest4

0.031

ClinPred

0.0070

GERP RS

-0.30

Varity_R

0.063

gMVP

0.015

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