Variant X-141905074-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_005462.5(MAGEC1):c.2T>C(p.Met1?) variant causes a start lost, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00395 in 1,210,682 control chromosomes in the GnomAD database, including 9 homozygotes. There are 1,495 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0031 ( 2 hom., 111 hem., cov: 23)

Exomes 𝑓: 0.0040 ( 7 hom. 1384 hem. )

Consequence

MAGEC1
NM_005462.5 start_lost, splice_region

Scores

Splicing: ADA: 0.00001205

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -1.45

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant X-141905074-T-C is Benign according to our data. Variant chrX-141905074-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1679865.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-141905074-T-C is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEC1	NM_005462.5 linkuse as main transcript	c.2T>C	p.Met1?	start_lost, splice_region_variant	3/4	ENST00000285879.5	NP_005453.2
MAGEC1	XM_011531418.3 linkuse as main transcript	c.2T>C	p.Met1?	start_lost, splice_region_variant	3/4		XP_011529720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEC1	ENST00000285879.5 linkuse as main transcript	c.2T>C	p.Met1?	start_lost, splice_region_variant	3/4	1	NM_005462.5	ENSP00000285879	P3	O60732-1
MAGEC1	ENST00000406005.2 linkuse as main transcript	c.-256T>C		splice_region_variant, 5_prime_UTR_variant	2/4	1		ENSP00000385500	A2	O60732-2

Frequencies

GnomAD3 genomes

AF:

0.00312

AC:

351

AN:

112437

Hom.:

Cov.:

AF XY:

0.00318

AC XY:

110

AN XY:

34607

show subpopulations

Gnomad AFR

AF:

0.000679

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00168

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000742

Gnomad FIN

AF:

0.00898

Gnomad MID

AF:

0.00422

Gnomad NFE

AF:

0.00470

Gnomad OTH

AF:

0.00197

GnomAD3 exomes

AF:

0.00334

AC:

612

AN:

183453

Hom.:

AF XY:

0.00348

AC XY:

236

AN XY:

67891

show subpopulations

Gnomad AFR exome

AF:

0.000608

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00110

Gnomad FIN exome

AF:

0.0102

Gnomad NFE exome

AF:

0.00455

Gnomad OTH exome

AF:

0.00353

GnomAD4 exome

AF:

0.00403

AC:

4427

AN:

1098192

Hom.:

Cov.:

AF XY:

0.00381

AC XY:

1384

AN XY:

363558

show subpopulations

Gnomad4 AFR exome

AF:

0.000341

Gnomad4 AMR exome

AF:

0.00139

Gnomad4 ASJ exome

AF:

0.000103

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00118

Gnomad4 FIN exome

AF:

0.00866

Gnomad4 NFE exome

AF:

0.00448

Gnomad4 OTH exome

AF:

0.00377

GnomAD4 genome

AF:

0.00313

AC:

352

AN:

112490

Hom.:

Cov.:

AF XY:

0.00320

AC XY:

111

AN XY:

34670

show subpopulations

Gnomad4 AFR

AF:

0.000678

Gnomad4 AMR

AF:

0.00167

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000744

Gnomad4 FIN

AF:

0.00898

Gnomad4 NFE

AF:

0.00472

Gnomad4 OTH

AF:

0.00195

Alfa

AF:

0.00384

Hom.:

Bravo

AF:

0.00263

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00450

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00580

AC:

ExAC

AF:

0.00282

AC:

343

EpiCase

AF:

0.00365

EpiControl

AF:

0.00445

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Lymphopenia;C0853697:Neutropenia

Benign:1

Likely benign, no assertion criteria provided

research

Department of Biosciences, University of Milan

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.2

DANN

Benign

0.37

DEOGEN2

Benign

0.0032

FATHMM_MKL

Benign

0.011

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.00071

MetaRNN

Benign

0.0082

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-0.14

REVEL

Benign

0.13

Sift

Pathogenic

0.0

Sift4G

Benign

0.076

Polyphen

0.46

Vest4

0.11

MVP

0.17

ClinPred

0.016

GERP RS

-1.8

Varity_R

0.68

gMVP

0.081

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000012

dbscSNV1_RF

Benign

0.0020

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