Variant X-141905574-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000285879.5(MAGEC1):c.170G>T(p.Arg57Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000507 in 1,203,431 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 20 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000038 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000052 ( 0 hom. 19 hem. )

Consequence

MAGEC1
ENST00000285879.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.55

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=0.044742197).

BS2

High Hemizygotes in GnomAdExome4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEC1	NM_005462.5 linkuse as main transcript	c.170G>T	p.Arg57Leu	missense_variant	4/4	ENST00000285879.5	NP_005453.2
MAGEC1	XM_011531418.3 linkuse as main transcript	c.170G>T	p.Arg57Leu	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.170G>T	p.Arg57Leu	missense_variant	4/4	1	NM_005462.5	ENSP00000285879	P3	O60732-1
MAGEC1	ENST00000406005.2 linkuse as main transcript	c.-115+27G>T		intron_variant		1		ENSP00000385500	A2	O60732-2

Frequencies

GnomAD3 genomes

AF:

0.0000375

AC:

AN:

106664

Hom.:

Cov.:

AF XY:

0.0000332

AC XY:

AN XY:

30110

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000775

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000382

AC:

AN:

183221

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

67739

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000856

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000520

AC:

AN:

1096767

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

363199

show subpopulations

Gnomad4 AFR exome

AF:

0.0000387

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000665

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000375

AC:

AN:

106664

Hom.:

Cov.:

AF XY:

0.0000332

AC XY:

AN XY:

30110

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000775

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Dec 17, 2023

The c.170G>T (p.R57L) alteration is located in exon 4 (coding exon 2) of the MAGEC1 gene. This alteration results from a G to T substitution at nucleotide position 170, causing the arginine (R) at amino acid position 57 to be replaced by a leucine (L). 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

0.15

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.043

DANN

Benign

0.49

DEOGEN2

Benign

0.0040

FATHMM_MKL

Benign

0.0087

LIST_S2

Benign

0.39

M_CAP

Benign

0.0077

MetaRNN

Benign

0.045

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.40

PROVEAN

Benign

0.10

REVEL

Benign

0.047

Sift

Uncertain

0.014

Sift4G

Benign

0.26

Polyphen

0.26

Vest4

0.055

MVP

0.040

ClinPred

0.055

GERP RS

-0.30

Varity_R

0.069

gMVP

0.038

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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