X-141905856-C-T

Variant names:

• chrX-141905856-C-T
• rs176037
• NM_005462.5:c.452C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005462.5(MAGEC1):​c.452C>T​(p.Thr151Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,197,229 control chromosomes in the GnomAD database, including 77,725 homozygotes. There are 165,329 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (5747 hom., 11523 hem., cov: 23)
  • Exomes 𝑓: 0.43 (71978 hom. 153806 hem.)
• Consequence: MAGEC1 NM_005462.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.627
• Publications: 24 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012508154).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEC1	NM_005462.5	MANE Select	c.452C>T	p.Thr151Ile	missense	Exon 4 of 4	NP_005453.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEC1	ENST00000285879.5	TSL:1 MANE Select	c.452C>T	p.Thr151Ile	missense	Exon 4 of 4	ENSP00000285879.4
	MAGEC1	ENST00000406005.2	TSL:1	c.-115+309C>T		intron	N/A	ENSP00000385500.2

Frequencies

GnomAD3 genomes AF: 0.367 AC: 40307 AN: 109915 Hom.: 5751 Cov.: 23

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.335

GnomAD2 exomes AF: 0.379 AC: 61196 AN: 161287 AF XY: 0.400

Gnomad AFR exome AF: 0.238

Gnomad AMR exome AF: 0.301

Gnomad ASJ exome AF: 0.411

Gnomad EAS exome AF: 0.171

Gnomad FIN exome AF: 0.457

Gnomad NFE exome AF: 0.475

Gnomad OTH exome AF: 0.398

GnomAD4 exome AF: 0.433 AC: 470724 AN: 1087261 Hom.: 71978 Cov.: 52 AF XY: 0.426 AC XY: 153806 AN XY: 361399

African (AFR) AF: 0.238 AC: 6158 AN: 25926

American (AMR) AF: 0.311 AC: 10855 AN: 34865

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 7859 AN: 19223

East Asian (EAS) AF: 0.191 AC: 5718 AN: 29950

South Asian (SAS) AF: 0.254 AC: 13509 AN: 53201

European-Finnish (FIN) AF: 0.425 AC: 16982 AN: 39949

Middle Eastern (MID) AF: 0.334 AC: 1365 AN: 4091

European-Non Finnish (NFE) AF: 0.467 AC: 389950 AN: 834641

Other (OTH) AF: 0.404 AC: 18328 AN: 45415

GnomAD4 genome AF: 0.366 AC: 40292 AN: 109968 Hom.: 5747 Cov.: 23 AF XY: 0.351 AC XY: 11523 AN XY: 32812

African (AFR) AF: 0.248 AC: 7518 AN: 30316

American (AMR) AF: 0.327 AC: 3426 AN: 10467

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1035 AN: 2615

East Asian (EAS) AF: 0.187 AC: 649 AN: 3466

South Asian (SAS) AF: 0.244 AC: 629 AN: 2577

European-Finnish (FIN) AF: 0.406 AC: 2366 AN: 5823

Middle Eastern (MID) AF: 0.367 AC: 79 AN: 215

European-Non Finnish (NFE) AF: 0.457 AC: 23906 AN: 52298

Other (OTH) AF: 0.333 AC: 506 AN: 1519

Alfa AF: 0.114 Hom.: 367

Bravo AF: 0.359

TwinsUK AF: 0.465 AC: 1724

ALSPAC AF: 0.468 AC: 1351

ESP6500AA AF: 0.260 AC: 997

ESP6500EA AF: 0.453 AC: 3046

ExAC AF: 0.371 AC: 44694

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.97	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.4
DANN	Benign	0.27
DEOGEN2	Benign	0.0030	T
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.63
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.066
Sift	Benign	0.43	T
Sift4G	Uncertain	0.021	D
Polyphen		0.90	P
Vest4		0.025
ClinPred		0.010	T
Varity_R		0.050
gMVP		0.027
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: rs176037; hg19: chrX-140993642; COSMIC: COSV53574821;