Variant rs56256227 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_005462.5(MAGEC1):c.2125C>T(p.His709Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.099 in 1,198,380 control chromosomes in the GnomAD database, including 4,117 homozygotes. There are 38,696 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.086 ( 319 hom., 2363 hem., cov: 21)

Exomes 𝑓: 0.10 ( 3798 hom. 36333 hem. )

Consequence

MAGEC1
NM_005462.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.40

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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEC1	NM_005462.5 link	c.2125C>T	p.His709Tyr	missense_variant	4/4	ENST00000285879.5	NP_005453.2	O60732-1
MAGEC1	XM_011531418.3 link	c.2125C>T	p.His709Tyr	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 link	c.2125C>T	p.His709Tyr	missense_variant	4/4	1	NM_005462.5	ENSP00000285879.4		O60732-1
MAGEC1	ENST00000406005.2 link	c.-114-561C>T		intron_variant		1		ENSP00000385500.2		O60732-2

Frequencies

GnomAD3 genomes

AF:

0.0861

AC:

9160

AN:

106388

Hom.:

320

Cov.:

AF XY:

0.0787

AC XY:

2357

AN XY:

29948

show subpopulations

Gnomad AFR

AF:

0.0711

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0685

Gnomad ASJ

AF:

0.0341

Gnomad EAS

AF:

0.0485

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.0871

Gnomad MID

AF:

0.0644

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.0873

GnomAD3 exomes

AF:

0.0912

AC:

16309

AN:

178747

Hom.:

518

AF XY:

0.0944

AC XY:

6017

AN XY:

63769

show subpopulations

Gnomad AFR exome

AF:

0.0687

Gnomad AMR exome

AF:

0.0901

Gnomad ASJ exome

AF:

0.0396

Gnomad EAS exome

AF:

0.0460

Gnomad SAS exome

AF:

0.133

Gnomad FIN exome

AF:

0.0907

Gnomad NFE exome

AF:

0.0985

Gnomad OTH exome

AF:

0.0829

GnomAD4 exome

AF:

0.100

AC:

109480

AN:

1091943

Hom.:

3798

Cov.:

AF XY:

0.101

AC XY:

36333

AN XY:

358027

show subpopulations

Gnomad4 AFR exome

AF:

0.0766

Gnomad4 AMR exome

AF:

0.0895

Gnomad4 ASJ exome

AF:

0.0400

Gnomad4 EAS exome

AF:

0.0468

Gnomad4 SAS exome

AF:

0.135

Gnomad4 FIN exome

AF:

0.0918

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.0890

GnomAD4 genome

AF:

0.0861

AC:

9159

AN:

106437

Hom.:

319

Cov.:

AF XY:

0.0788

AC XY:

2363

AN XY:

30005

show subpopulations

Gnomad4 AFR

AF:

0.0712

Gnomad4 AMR

AF:

0.0681

Gnomad4 ASJ

AF:

0.0341

Gnomad4 EAS

AF:

0.0487

Gnomad4 SAS

AF:

0.126

Gnomad4 FIN

AF:

0.0871

Gnomad4 NFE

AF:

0.102

Gnomad4 OTH

AF:

0.0861

Alfa

AF:

0.0933

Hom.:

3430

Bravo

AF:

0.0818

TwinsUK

AF:

0.100

AC:

371

ALSPAC

AF:

0.100

AC:

290

ESP6500AA

AF:

0.0686

AC:

263

ESP6500EA

AF:

0.0985

AC:

663

ExAC

AF:

0.0932

AC:

11314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-1.1

BayesDel_noAF

Benign

-1.2

CADD

Benign

0.18

DANN

Benign

0.48

DEOGEN2

Benign

0.0033

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.23

MetaRNN

Benign

0.0025

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.69

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.34

REVEL

Benign

0.059

Sift

Benign

0.16

Sift4G

Benign

0.23

Polyphen

0.0010

Vest4

0.020

ClinPred

0.00058

GERP RS

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.95

Varity_R

0.043

gMVP

0.011

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: 12

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