chrX-141906015-GCTCCTTCTCCTCCACTTTATTGAGTATTTTCCAGAGTTCCCCTGAGAGAACTCAGAGTACTTTTGAGGGTTTTGCCCAGTCTCCTCTCCAGATTCCTGTGAGCCCCTCCTCCTCCTCCACTTTACTGAGTCTTTTCCAGAGTTTCTCTGAGAGAACTCAGAGTACTTTTGAGGGTTTTGCCCAGTCTTCTCTCCAGATTCCTGTGAGCCC-G

Position:

• chrX-141906015-GCTCCTTCTCCTCCACTTTATTGAGTATTTTCCAGAGTTCCCCTGAGAGAACTCAGAGTACTTTTGAGGGTTTTGCCCAGTCTCCTCTCCAGATTCCTGTGAGCCCCTCCTCCTCCTCCACTTTACTGAGTCTTTTCCAGAGTTTCTCTGAGAGAACTCAGAGTACTTTTGAGGGTTTTGCCCAGTCTTCTCTCCAGATTCCTGTGAGCCC-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS2

The NM_005462.5(MAGEC1):​c.631_840del​(p.Leu211_Leu280del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00578 in 107,519 control chromosomes in the GnomAD database, including 1 homozygotes. There are 26 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0058 (1 hom., 26 hem., cov: 34)
  • Exomes 𝑓: 0.0046 (56 hom. 1564 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAGEC1 NM_005462.5 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.77

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 -4 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_005462.5.
• BP6: Variant X-141906015-GCTCCTTCTCCTCCACTTTATTGAGTATTTTCCAGAGTTCCCCTGAGAGAACTCAGAGTACTTTTGAGGGTTTTGCCCAGTCTCCTCTCCAGATTCCTGTGAGCCCCTCCTCCTCCTCCACTTTACTGAGTCTTTTCCAGAGTTTCTCTGAGAGAACTCAGAGTACTTTTGAGGGTTTTGCCCAGTCTTCTCTCCAGATTCCTGTGAGCCC-G is Benign according to our data. Variant chrX-141906015-GCTCCTTCTCCTCCACTTTATTGAGTATTTTCCAGAGTTCCCCTGAGAGAACTCAGAGTACTTTTGAGGGTTTTGCCCAGTCTCCTCTCCAGATTCCTGTGAGCCCCTCCTCCTCCTCCACTTTACTGAGTCTTTTCCAGAGTTTCTCTGAGAGAACTCAGAGTACTTTTGAGGGTTTTGCCCAGTCTTCTCTCCAGATTCCTGTGAGCCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 2661554.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 26 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEC1	NM_005462.5	c.631_840del	p.Leu211_Leu280del	inframe_deletion	4/4	ENST00000285879.5	NP_005453.2
MAGEC1	XM_011531418.3	c.631_840del	p.Leu211_Leu280del	inframe_deletion	4/4		XP_011529720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEC1	ENST00000285879.5	c.631_840del	p.Leu211_Leu280del	inframe_deletion	4/4	1	NM_005462.5	ENSP00000285879	P3
MAGEC1	ENST00000406005.2	c.-115+488_-115+697del		intron_variant		1		ENSP00000385500	A2

Frequencies

GnomAD3 genomes AF: 0.00579 AC: 622 AN: 107468 Hom.: 1 Cov.: 34 AF XY: 0.000797 AC XY: 26 AN XY: 32614

Gnomad AFR AF: 0.000881

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00487

Gnomad ASJ AF: 0.0281

Gnomad EAS AF: 0.000330

Gnomad SAS AF: 0.00116

Gnomad FIN AF: 0.00185

Gnomad MID AF: 0.0145

Gnomad NFE AF: 0.00872

Gnomad OTH AF: 0.00559

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00465 AC: 5038 AN: 1084562 Hom.: 56 AF XY: 0.00436 AC XY: 1564 AN XY: 358672

Gnomad4 AFR exome AF: 0.000779

Gnomad4 AMR exome AF: 0.00363

Gnomad4 ASJ exome AF: 0.0232

Gnomad4 EAS exome AF: 0.0000724

Gnomad4 SAS exome AF: 0.000804

Gnomad4 FIN exome AF: 0.00144

Gnomad4 NFE exome AF: 0.00492

Gnomad4 OTH exome AF: 0.00477

GnomAD4 genome AF: 0.00578 AC: 621 AN: 107519 Hom.: 1 Cov.: 34 AF XY: 0.000796 AC XY: 26 AN XY: 32671

Gnomad4 AFR AF: 0.000879

Gnomad4 AMR AF: 0.00487

Gnomad4 ASJ AF: 0.0281

Gnomad4 EAS AF: 0.000331

Gnomad4 SAS AF: 0.00116

Gnomad4 FIN AF: 0.00185

Gnomad4 NFE AF: 0.00870

Gnomad4 OTH AF: 0.00551

Alfa AF: 0.00112 Hom.: 0

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

Mar 01, 2023

MAGEC1: BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1569477350; hg19: chrX-140993801;