Genetic Variant MAGEC1:p.Ala229Ala (chrX-141906091-C-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_005462.5(MAGEC1):c.687C>A(p.Ala229Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.41 ( 131 hom., 577 hem., cov: 18)

Exomes 𝑓: 0.36 ( 2418 hom. 8894 hem. )

Failed GnomAD Quality Control

Consequence

MAGEC1
NM_005462.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.868

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 Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant X-141906091-C-A is Benign according to our data. Variant chrX-141906091-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2605077.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.868 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEC1	NM_005462.5 link	c.687C>A	p.Ala229Ala	synonymous_variant	Exon 4 of 4	ENST00000285879.5	NP_005453.2	O60732-1
MAGEC1	XM_011531418.3 link	c.687C>A	p.Ala229Ala	synonymous_variant	Exon 4 of 4		XP_011529720.1	O60732-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGEC1	ENST00000285879.5 link	c.687C>A	p.Ala229Ala	synonymous_variant	Exon 4 of 4	1	NM_005462.5	ENSP00000285879.4		O60732-1
MAGEC1	ENST00000406005.2 link	c.-115+544C>A		intron_variant	Intron 3 of 3	1		ENSP00000385500.2		O60732-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

20242

AN:

48995

Hom.:

130

Cov.:

AF XY:

0.102

AC XY:

573

AN XY:

5633

FAILED QC

Gnomad AFR

AF:

0.460

Gnomad AMI

AF:

0.355

Gnomad AMR

AF:

0.436

Gnomad ASJ

AF:

0.410

Gnomad EAS

AF:

0.325

Gnomad SAS

AF:

0.253

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.360

Gnomad NFE

AF:

0.411

Gnomad OTH

AF:

0.402

GnomAD3 exomes

AF:

0.311

AC:

16880

AN:

54316

Hom.:

150

AF XY:

0.0736

AC XY:

1115

AN XY:

15148

show subpopulations

Gnomad AFR exome

AF:

0.401

Gnomad AMR exome

AF:

0.399

Gnomad ASJ exome

AF:

0.320

Gnomad EAS exome

AF:

0.206

Gnomad SAS exome

AF:

0.150

Gnomad FIN exome

AF:

0.315

Gnomad NFE exome

AF:

0.324

Gnomad OTH exome

AF:

0.304

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.365

AC:

159022

AN:

435733

Hom.:

2418

Cov.:

AF XY:

0.112

AC XY:

8894

AN XY:

79677

show subpopulations

Gnomad4 AFR exome

AF:

0.421

Gnomad4 AMR exome

AF:

0.414

Gnomad4 ASJ exome

AF:

0.342

Gnomad4 EAS exome

AF:

0.188

Gnomad4 SAS exome

AF:

0.198

Gnomad4 FIN exome

AF:

0.262

Gnomad4 NFE exome

AF:

0.379

Gnomad4 OTH exome

AF:

0.346

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.413

AC:

20241

AN:

48993

Hom.:

131

Cov.:

AF XY:

0.102

AC XY:

577

AN XY:

5653

show subpopulations

Gnomad4 AFR

AF:

0.460

Gnomad4 AMR

AF:

0.436

Gnomad4 ASJ

AF:

0.410

Gnomad4 EAS

AF:

0.325

Gnomad4 SAS

AF:

0.254

Gnomad4 FIN

AF:

0.280

Gnomad4 NFE

AF:

0.411

Gnomad4 OTH

AF:

0.406

Alfa

AF:

0.00659

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jun 21, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.4

DANN

Benign

0.32

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