X-141906125-TC-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_005462.5(MAGEC1):c.723del(p.Ser242ProfsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00059 (2 hom., 6 hem., cov: 9)
  • Exomes 𝑓: 0.000010 (0 hom. 2 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAGEC1 NM_005462.5 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.253

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant X-141906125-TC-T is Benign according to our data. Variant chrX-141906125-TC-T is described in ClinVar as [Likely_benign]. Clinvar id is 3234566.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGEC1	NM_005462.5	c.723del	p.Ser242ProfsTer5	frameshift_variant	4/4	ENST00000285879.5
MAGEC1	XM_011531418.3	c.723del	p.Ser242ProfsTer5	frameshift_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGEC1	ENST00000285879.5	c.723del	p.Ser242ProfsTer5	frameshift_variant	4/4	1	NM_005462.5	P3
MAGEC1	ENST00000406005.2	c.-115+580del		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.000587 AC: 57 AN: 97094 Hom.: 2 Cov.: 9 AF XY: 0.000239 AC XY: 6 AN XY: 25114

Gnomad AFR AF: 0.00188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000326

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000432

Gnomad OTH AF: 0.000773

GnomAD3 exomes AF: 0.0000801 AC: 14 AN: 174768 Hom.: 0 AF XY: 0.0000975 AC XY: 6 AN XY: 61528

Gnomad AFR exome AF: 0.00103

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000148

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000101 AC: 7 AN: 691997 Hom.: 0 Cov.: 33 AF XY: 0.00000992 AC XY: 2 AN XY: 201527

Gnomad4 AFR exome AF: 0.000241

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000296

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000308

GnomAD4 genome AF: 0.000587 AC: 57 AN: 97130 Hom.: 2 Cov.: 9 AF XY: 0.000238 AC XY: 6 AN XY: 25158

Gnomad4 AFR AF: 0.00188

Gnomad4 AMR AF: 0.000326

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000432

Gnomad4 OTH AF: 0.000763

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

MAGEC1: BS2 -

Computational scores

Source: dbNSFP v4.3

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: rs745821213; hg19: chrX-140993911;