Variant X-141905951-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005462.5(MAGEC1):c.547C>T(p.Pro183Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000914 in 1,203,851 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 28)

Exomes 𝑓: 0.0000082 ( 0 hom. 3 hem. )

Consequence

MAGEC1
NM_005462.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.216

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=0.050805688).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEC1	NM_005462.5 link	c.547C>T	p.Pro183Ser	missense_variant	4/4	ENST00000285879.5	NP_005453.2	O60732-1
MAGEC1	XM_011531418.3 link	c.547C>T	p.Pro183Ser	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.547C>T	p.Pro183Ser	missense_variant	4/4	1	NM_005462.5	ENSP00000285879.4		O60732-1
MAGEC1	ENST00000406005.2 link	c.-115+404C>T		intron_variant		1		ENSP00000385500.2		O60732-2

Frequencies

GnomAD3 genomes

AF:

0.0000177

AC:

AN:

112763

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35063

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:

0.000281

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000654

GnomAD3 exomes

AF:

0.00000547

AC:

AN:

182785

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67661

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000722

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:

0.00000825

AC:

AN:

1091088

Hom.:

Cov.:

AF XY:

0.00000830

AC XY:

AN XY:

361484

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000288

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000335

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000596

Gnomad4 OTH exome

AF:

0.0000438

GnomAD4 genome

AF:

0.0000177

AC:

AN:

112763

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35063

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000281

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000654

ExAC

AF:

0.00000826

AC:

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

Jan 09, 2024

The c.547C>T (p.P183S) alteration is located in exon 4 (coding exon 2) of the MAGEC1 gene. This alteration results from a C to T substitution at nucleotide position 547, causing the proline (P) at amino acid position 183 to be replaced by a serine (S). 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

0.18

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.86

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0060

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.31

M_CAP

Benign

0.0056

MetaRNN

Benign

0.051

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.34

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.5

REVEL

Benign

0.050

Sift

Pathogenic

0.0

Sift4G

Benign

0.085

Polyphen

0.020

Vest4

0.094

MutPred

0.20

Gain of phosphorylation at P183 (P = 0.0178);

MVP

0.048

ClinPred

0.21

Varity_R

0.070

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over