Variant X-141906098-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005462.5(MAGEC1):c.694C>G(p.Pro232Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.000010 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000018 ( 0 hom. 7 hem. )

Failed GnomAD Quality Control

Consequence

MAGEC1
NM_005462.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.39

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.049833655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGEC1	NM_005462.5 linkuse as main transcript	c.694C>G	p.Pro232Ala	missense_variant	4/4	ENST00000285879.5
MAGEC1	XM_011531418.3 linkuse as main transcript	c.694C>G	p.Pro232Ala	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGEC1	ENST00000285879.5 linkuse as main transcript	c.694C>G	p.Pro232Ala	missense_variant	4/4	1	NM_005462.5	P3	O60732-1
MAGEC1	ENST00000406005.2 linkuse as main transcript	c.-115+551C>G		intron_variant		1		A2	O60732-2

Frequencies

GnomAD3 genomes

AF:

0.0000101

AC:

AN:

98770

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

29400

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000110

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

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000184

AC:

AN:

926242

Hom.:

Cov.:

AF XY:

0.0000230

AC XY:

AN XY:

303732

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000878

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000169

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000101

AC:

AN:

98770

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

29400

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000110

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

ExAC

AF:

0.0000406

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

Aug 10, 2021

The c.694C>G (p.P232A) alteration is located in exon 4 (coding exon 2) of the MAGEC1 gene. This alteration results from a C to G substitution at nucleotide position 694, causing the proline (P) at amino acid position 232 to be replaced by an alanine (A). 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

-0.45

BayesDel_noAF

Benign

-0.88

Cadd

Benign

4.9

Dann

Benign

0.50

DEOGEN2

Benign

0.0063

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.40

M_CAP

Benign

0.0047

MetaRNN

Benign

0.050

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.72

REVEL

Benign

0.023

Sift

Uncertain

0.0030

Sift4G

Benign

0.29

Polyphen

0.012

Vest4

0.062

MVP

0.055

ClinPred

0.56

Varity_R

0.048

gMVP

0.0098

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