NM_005462.5:c.74G>A

Variant names:

• chrX-141905478-G-A
• rs176036
• NM_005462.5:c.74G>A

Variant summary

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

The NM_005462.5(MAGEC1):​c.74G>A​(p.Cys25Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,209,037 control chromosomes in the GnomAD database, including 18,094 homozygotes. There are 77,651 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.18 (1386 hom., 5551 hem., cov: 23)
  • Exomes 𝑓: 0.20 (16708 hom. 72100 hem.)
• Consequence: MAGEC1 NM_005462.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.29
• Publications: 13 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=0.0052823722).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 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.74G>A	p.Cys25Tyr	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.74G>A	p.Cys25Tyr	missense	Exon 4 of 4	ENSP00000285879.4
	MAGEC1	ENST00000406005.2	TSL:1	c.-184G>A		5_prime_UTR	Exon 3 of 4	ENSP00000385500.2

Frequencies

GnomAD3 genomes AF: 0.179 AC: 19926 AN: 111577 Hom.: 1388 Cov.: 23

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.0642

Gnomad SAS AF: 0.0514

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.216

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.167

GnomAD2 exomes AF: 0.177 AC: 32328 AN: 183042 AF XY: 0.171

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.198

Gnomad ASJ exome AF: 0.201

Gnomad EAS exome AF: 0.0652

Gnomad FIN exome AF: 0.179

Gnomad NFE exome AF: 0.216

Gnomad OTH exome AF: 0.187

GnomAD4 exome AF: 0.205 AC: 224711 AN: 1097406 Hom.: 16708 Cov.: 34 AF XY: 0.199 AC XY: 72100 AN XY: 362846

African (AFR) AF: 0.145 AC: 3815 AN: 26387

American (AMR) AF: 0.195 AC: 6874 AN: 35202

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 3796 AN: 19370

East Asian (EAS) AF: 0.0720 AC: 2175 AN: 30201

South Asian (SAS) AF: 0.0637 AC: 3449 AN: 54134

European-Finnish (FIN) AF: 0.182 AC: 7370 AN: 40519

Middle Eastern (MID) AF: 0.173 AC: 714 AN: 4136

European-Non Finnish (NFE) AF: 0.223 AC: 187810 AN: 841396

Other (OTH) AF: 0.189 AC: 8708 AN: 46061

GnomAD4 genome AF: 0.178 AC: 19919 AN: 111631 Hom.: 1386 Cov.: 23 AF XY: 0.164 AC XY: 5551 AN XY: 33881

African (AFR) AF: 0.151 AC: 4649 AN: 30727

American (AMR) AF: 0.169 AC: 1804 AN: 10650

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 484 AN: 2637

East Asian (EAS) AF: 0.0644 AC: 226 AN: 3510

South Asian (SAS) AF: 0.0504 AC: 134 AN: 2657

European-Finnish (FIN) AF: 0.169 AC: 1030 AN: 6085

Middle Eastern (MID) AF: 0.209 AC: 45 AN: 215

European-Non Finnish (NFE) AF: 0.212 AC: 11224 AN: 52947

Other (OTH) AF: 0.167 AC: 254 AN: 1519

Alfa AF: 0.192 Hom.: 11348

Bravo AF: 0.181

TwinsUK AF: 0.214 AC: 793

ALSPAC AF: 0.216 AC: 625

ESP6500AA AF: 0.160 AC: 612

ESP6500EA AF: 0.208 AC: 1399

ExAC AF: 0.173 AC: 21001

EpiCase AF: 0.214

EpiControl AF: 0.209

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.88	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.65
DEOGEN2	Benign	0.0030	T
FATHMM_MKL	Benign	0.0070	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	0.0053	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	N
PhyloP100		-3.3
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.095
Sift	Benign	0.15	T
Sift4G	Benign	1.0	T
Polyphen		0.80	P
Vest4		0.031
ClinPred		0.0070	T
GERP RS		-0.30
Varity_R		0.063
gMVP		0.015
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: rs176036; hg19: chrX-140993264; COSMIC: COSV53572823;