Variant X-141905814-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_005462.5(MAGEC1):c.410C>G(p.Ser137Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,098,195 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.000027 ( 0 hom. 11 hem. )

Consequence

MAGEC1
NM_005462.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.72

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=0.17599866).

BP6

Variant X-141905814-C-G is Benign according to our data. Variant chrX-141905814-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3026261.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEC1	NM_005462.5 link	c.410C>G	p.Ser137Cys	missense_variant	4/4	ENST00000285879.5	NP_005453.2	O60732-1
MAGEC1	XM_011531418.3 link	c.410C>G	p.Ser137Cys	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.410C>G	p.Ser137Cys	missense_variant	4/4	1	NM_005462.5	ENSP00000285879.4		O60732-1
MAGEC1	ENST00000406005.2 link	c.-115+267C>G		intron_variant		1		ENSP00000385500.2		O60732-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000273

AC:

AN:

183481

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

67913

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:

0.0000610

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000273

AC:

AN:

1098195

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

363559

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

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:

0.0000321

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

MAGEC1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.54

DEOGEN2

Benign

0.0042

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.29

M_CAP

Benign

0.023

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.76

MutationAssessor

Benign

0.97

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.95

REVEL

Benign

0.048

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

0.88

Vest4

0.27

MutPred

0.38

Loss of phosphorylation at S137 (P = 0.0277);

MVP

0.061

ClinPred

0.14

Varity_R

0.12

gMVP

0.017

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over