Genetic Variant MAGEC1:p.Pro197Ser (chrX-141905993-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.589C>T(p.Pro197Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,206,478 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 34)

Exomes 𝑓: 0.000011 ( 0 hom. 2 hem. )

Consequence

MAGEC1
NM_005462.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0760

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=0.048368365).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEC1	NM_005462.5 link	c.589C>T	p.Pro197Ser	missense_variant	Exon 4 of 4	ENST00000285879.5	NP_005453.2	O60732-1
MAGEC1	XM_011531418.3 link	c.589C>T	p.Pro197Ser	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.589C>T	p.Pro197Ser	missense_variant	Exon 4 of 4	1	NM_005462.5	ENSP00000285879.4		O60732-1
MAGEC1	ENST00000406005.2 link	c.-115+446C>T		intron_variant	Intron 3 of 3	1		ENSP00000385500.2		O60732-2

Frequencies

GnomAD3 genomes

AF:

0.0000176

AC:

AN:

113380

Hom.:

Cov.:

AF XY:

0.0000279

AC XY:

AN XY:

35788

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:

0.000158

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000187

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000547

AC:

AN:

182941

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67745

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:

0.0000525

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1093048

Hom.:

Cov.:

103

AF XY:

0.00000552

AC XY:

AN XY:

362008

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000186

Gnomad4 FIN exome

AF:

0.0000253

Gnomad4 NFE exome

AF:

0.0000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000176

AC:

AN:

113430

Hom.:

Cov.:

AF XY:

0.0000279

AC XY:

AN XY:

35850

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:

0.000158

Gnomad4 NFE

AF:

0.0000187

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000248

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.93

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.0057

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.39

M_CAP

Benign

0.021

MetaRNN

Benign

0.048

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.97

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.6

REVEL

Benign

0.078

Sift

Pathogenic

0.0

Sift4G

Benign

0.91

Polyphen

0.0040

Vest4

0.042

MVP

0.048

ClinPred

0.16

Varity_R

0.063

gMVP

0.025

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