Variant X-141906005-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005462.5(MAGEC1):c.601C>A(p.Pro201Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 0.000045 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

MAGEC1
NM_005462.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.788

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.066289335).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEC1	NM_005462.5 link	c.601C>A	p.Pro201Thr	missense_variant	4/4	ENST00000285879.5	NP_005453.2	O60732-1
MAGEC1	XM_011531418.3 link	c.601C>A	p.Pro201Thr	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.601C>A	p.Pro201Thr	missense_variant	4/4	1	NM_005462.5	ENSP00000285879.4		O60732-1
MAGEC1	ENST00000406005.2 link	c.-115+458C>A		intron_variant		1		ENSP00000385500.2		O60732-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000545

AC:

AN:

183355

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67865

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:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000447

AC:

AN:

1095070

Hom.:

Cov.:

108

AF XY:

0.00

AC XY:

AN XY:

362492

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000286

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:

0.0000512

Gnomad4 OTH exome

AF:

0.0000872

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000843

Hom.:

ExAC

AF:

0.0000578

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Sep 11, 2024

The c.601C>A (p.P201T) alteration is located in exon 4 (coding exon 2) of the MAGEC1 gene. This alteration results from a C to A substitution at nucleotide position 601, causing the proline (P) at amino acid position 201 to be replaced by a threonine (T). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.93

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.0056

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.39

M_CAP

Benign

0.012

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.5

REVEL

Benign

0.022

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0030

Polyphen

0.0070

Vest4

0.096

MVP

0.055

ClinPred

0.16

Varity_R

0.11

gMVP

0.035

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