X-141906091-C-A

Variant names:

• chrX-141906091-C-A
• rs176039
• NM_005462.5:c.687C>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.868
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 2605077.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.868 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005462.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEC1	NM_005462.5	MANE Select	c.687C>A	p.Ala229Ala	synonymous	Exon 4 of 4	NP_005453.2	O60732-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEC1	ENST00000285879.5	TSL:1 MANE Select	c.687C>A	p.Ala229Ala	synonymous	Exon 4 of 4	ENSP00000285879.4	O60732-1
	MAGEC1	ENST00000406005.2	TSL:1	c.-115+544C>A		intron	N/A	ENSP00000385500.2	O60732-2

Frequencies

GnomAD3 genomes AF: 0.413 AC: 20242 AN: 48995 Hom.: 130 Cov.: 18

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

GnomAD2 exomes AF: 0.311 AC: 16880 AN: 54316 AF XY: 0.0736

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.421 AC: 3806 AN: 9036

American (AMR) AF: 0.414 AC: 5374 AN: 12994

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1940 AN: 5673

East Asian (EAS) AF: 0.188 AC: 1500 AN: 7960

South Asian (SAS) AF: 0.198 AC: 3678 AN: 18565

European-Finnish (FIN) AF: 0.262 AC: 2847 AN: 10855

Middle Eastern (MID) AF: 0.320 AC: 487 AN: 1522

European-Non Finnish (NFE) AF: 0.379 AC: 133885 AN: 353204

Other (OTH) AF: 0.346 AC: 5505 AN: 15924

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.460 AC: 5659 AN: 12301

American (AMR) AF: 0.436 AC: 2112 AN: 4847

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 487 AN: 1187

East Asian (EAS) AF: 0.325 AC: 545 AN: 1678

South Asian (SAS) AF: 0.254 AC: 253 AN: 996

European-Finnish (FIN) AF: 0.280 AC: 606 AN: 2164

Middle Eastern (MID) AF: 0.342 AC: 39 AN: 114

European-Non Finnish (NFE) AF: 0.411 AC: 10138 AN: 24673

Other (OTH) AF: 0.406 AC: 281 AN: 692

Alfa AF: 0.00659 Hom.: 1

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.32
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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