X-141906091-C-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_005462.5(MAGEC1):c.687C>A(p.Ala229=) 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.868

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]

ACMG classification

Verdict is Benign. Variant got -11 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.
• BS2: High Homozygotes in GnomAdExome at 150 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGEC1	NM_005462.5	c.687C>A	p.Ala229=	synonymous_variant	4/4	ENST00000285879.5
MAGEC1	XM_011531418.3	c.687C>A	p.Ala229=	synonymous_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGEC1	ENST00000285879.5	c.687C>A	p.Ala229=	synonymous_variant	4/4	1	NM_005462.5	P3
MAGEC1	ENST00000406005.2	c.-115+544C>A		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 20242 AN: 48995 Hom.: 130 Cov.: 18 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

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.: 69 AF XY: 0.112 AC XY: 8894 AN XY: 79677

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.: 18 AF XY: 0.102 AC XY: 577 AN XY: 5653

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.: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2023

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

Other links and lift over

dbSNP: rs176039; hg19: chrX-140993877; COSMIC: COSV53575809;