Genetic Variant MAGEC1:p.Leu443Phe (chrX-141906731-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_005462.5(MAGEC1):c.1327C>T(p.Leu443Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000865 in 1,201,863 control chromosomes in the GnomAD database, including 2 homozygotes. There are 24 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., 8 hem., cov: 22)

Exomes 𝑓: 0.000064 ( 2 hom. 16 hem. )

Consequence

MAGEC1
NM_005462.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.104

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.012540221).

BS2

High Hemizygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEC1	NM_005462.5 link	c.1327C>T	p.Leu443Phe	missense_variant	Exon 4 of 4	ENST00000285879.5	NP_005453.2	O60732-1
MAGEC1	XM_011531418.3 link	c.1327C>T	p.Leu443Phe	missense_variant	Exon 4 of 4		XP_011529720.1	O60732-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGEC1	ENST00000285879.5 link	c.1327C>T	p.Leu443Phe	missense_variant	Exon 4 of 4	1	NM_005462.5	ENSP00000285879.4		O60732-1
MAGEC1	ENST00000406005.2 link	c.-115+1184C>T		intron_variant	Intron 3 of 3	1		ENSP00000385500.2		O60732-2

Frequencies

GnomAD3 genomes

AF:

0.000311

AC:

AN:

109466

Hom.:

Cov.:

AF XY:

0.000248

AC XY:

AN XY:

32260

show subpopulations

Gnomad AFR

AF:

0.00115

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000989

AC:

AN:

182070

Hom.:

AF XY:

0.0000747

AC XY:

AN XY:

66928

show subpopulations

Gnomad AFR exome

AF:

0.00140

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000641

AC:

AN:

1092355

Hom.:

Cov.:

AF XY:

0.0000446

AC XY:

AN XY:

358711

show subpopulations

Gnomad4 AFR exome

AF:

0.00238

Gnomad4 AMR exome

AF:

0.0000570

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:

0.00000119

Gnomad4 OTH exome

AF:

0.000109

GnomAD4 genome

AF:

0.000310

AC:

AN:

109508

Hom.:

Cov.:

AF XY:

0.000248

AC XY:

AN XY:

32314

show subpopulations

Gnomad4 AFR

AF:

0.00115

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:

0.00

Gnomad4 OTH

AF:

0.00

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000116

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.98

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.0057

FATHMM_MKL

Benign

0.0083

LIST_S2

Benign

0.32

M_CAP

Benign

0.0015

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.90

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.50

REVEL

Benign

0.050

Sift

Pathogenic

0.0

Sift4G

Benign

0.19

Polyphen

0.98

Vest4

0.053

MutPred

0.14

Loss of catalytic residue at L443 (P = 0.1044);

MVP

0.088

ClinPred

0.072

GERP RS

0.13

Varity_R

0.14

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