rs12845617

Positions:

• chrX-141908578-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_005462.5(MAGEC1):​c.3174G>A​(p.Glu1058=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,201,785 control chromosomes in the GnomAD database, including 10,033 homozygotes. There are 61,860 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.14 (858 hom., 4678 hem., cov: 23)
  • Exomes 𝑓: 0.16 (9175 hom. 57182 hem.)
• Consequence: MAGEC1 NM_005462.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant X-141908578-G-A is Benign according to our data. Variant chrX-141908578-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.291 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGEC1	NM_005462.5	c.3174G>A	p.Glu1058=	synonymous_variant	4/4	ENST00000285879.5
MAGEC1	XM_011531418.3	c.3174G>A	p.Glu1058=	synonymous_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGEC1	ENST00000285879.5	c.3174G>A	p.Glu1058=	synonymous_variant	4/4	1	NM_005462.5	P3
MAGEC1	ENST00000406005.2	c.375G>A	p.Glu125=	synonymous_variant	4/4	1		A2

Frequencies

GnomAD3 genomes AF: 0.144 AC: 15917 AN: 110857 Hom.: 860 Cov.: 23 AF XY: 0.141 AC XY: 4676 AN XY: 33127

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0928

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.119

GnomAD3 exomes AF: 0.148 AC: 25829 AN: 174142 Hom.: 1287 AF XY: 0.153 AC XY: 9153 AN XY: 59686

Gnomad AFR exome AF: 0.120

Gnomad AMR exome AF: 0.0869

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.128

Gnomad SAS exome AF: 0.198

Gnomad FIN exome AF: 0.172

Gnomad NFE exome AF: 0.163

Gnomad OTH exome AF: 0.146

GnomAD4 exome AF: 0.158 AC: 171838 AN: 1090876 Hom.: 9175 Cov.: 34 AF XY: 0.160 AC XY: 57182 AN XY: 357648

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.0880

Gnomad4 ASJ exome AF: 0.146

Gnomad4 EAS exome AF: 0.129

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.177

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.144 AC: 15917 AN: 110909 Hom.: 858 Cov.: 23 AF XY: 0.141 AC XY: 4678 AN XY: 33189

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.118

Alfa AF: 0.150 Hom.: 1254

Bravo AF: 0.137

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.70
DANN	Benign	0.49

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: rs12845617; hg19: chrX-140996364; COSMIC: COSV53568157;