Variant X-141905973-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000285879.5(MAGEC1):c.569T>C(p.Phe190Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000257 in 1,206,824 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. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., 1 hem., cov: 34)

Exomes 𝑓: 0.000022 ( 0 hom. 10 hem. )

Consequence

MAGEC1
ENST00000285879.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.11

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=0.051816106).

BS2

High Hemizygotes in GnomAdExome4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEC1	NM_005462.5 linkuse as main transcript	c.569T>C	p.Phe190Ser	missense_variant	4/4	ENST00000285879.5	NP_005453.2
MAGEC1	XM_011531418.3 linkuse as main transcript	c.569T>C	p.Phe190Ser	missense_variant	4/4		XP_011529720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEC1	ENST00000285879.5 linkuse as main transcript	c.569T>C	p.Phe190Ser	missense_variant	4/4	1	NM_005462.5	ENSP00000285879	P3	O60732-1
MAGEC1	ENST00000406005.2 linkuse as main transcript	c.-115+426T>C		intron_variant		1		ENSP00000385500	A2	O60732-2

Frequencies

GnomAD3 genomes

AF:

0.0000618

AC:

AN:

113221

Hom.:

Cov.:

AF XY:

0.0000281

AC XY:

AN XY:

35551

show subpopulations

Gnomad AFR

AF:

0.0000958

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00114

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000360

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000548

AC:

AN:

182514

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67574

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:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1093603

Hom.:

Cov.:

102

AF XY:

0.0000276

AC XY:

AN XY:

362165

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000575

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000560

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000107

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000618

AC:

AN:

113221

Hom.:

Cov.:

AF XY:

0.0000281

AC XY:

AN XY:

35551

show subpopulations

Gnomad4 AFR

AF:

0.0000958

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00114

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000360

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000607

Hom.:

ExAC

AF:

0.000132

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

Jun 21, 2022

The c.569T>C (p.F190S) alteration is located in exon 4 (coding exon 2) of the MAGEC1 gene. This alteration results from a T to C substitution at nucleotide position 569, causing the phenylalanine (F) at amino acid position 190 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

Pathogenic

0.86

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.88

CADD

Benign

6.1

DANN

Benign

0.35

DEOGEN2

Benign

0.0050

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.23

M_CAP

Benign

0.0019

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.79

REVEL

Benign

0.049

Sift

Pathogenic

0.0

Sift4G

Benign

0.24

Polyphen

0.0020

Vest4

0.11

MutPred

0.19

Gain of phosphorylation at F190 (P = 0.013);

MVP

0.040

ClinPred

0.064

Varity_R

0.15

gMVP

0.028

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