rs176036

Positions:

• chrX-141905478-G-A
• chrX-141905478-G-C
• chrX-141905478-G-T

Variant summary

Our verdict is Benign. Variant got -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. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGEC1	NM_005462.5	c.74G>A	p.Cys25Tyr	missense_variant	4/4	ENST00000285879.5
MAGEC1	XM_011531418.3	c.74G>A	p.Cys25Tyr	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGEC1	ENST00000285879.5	c.74G>A	p.Cys25Tyr	missense_variant	4/4	1	NM_005462.5	P3
MAGEC1	ENST00000406005.2	c.-184G>A		5_prime_UTR_variant	3/4	1		A2

Frequencies

GnomAD3 genomes AF: 0.179 AC: 19926 AN: 111577 Hom.: 1388 Cov.: 23 AF XY: 0.164 AC XY: 5551 AN XY: 33817

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

GnomAD3 exomes AF: 0.177 AC: 32328 AN: 183042 Hom.: 1984 AF XY: 0.171 AC XY: 11542 AN XY: 67558

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 SAS exome AF: 0.0585

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

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.195

Gnomad4 ASJ exome AF: 0.196

Gnomad4 EAS exome AF: 0.0720

Gnomad4 SAS exome AF: 0.0637

Gnomad4 FIN exome AF: 0.182

Gnomad4 NFE exome AF: 0.223

Gnomad4 OTH exome AF: 0.189

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

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.0644

Gnomad4 SAS AF: 0.0504

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.167

Alfa AF: 0.194 Hom.: 10467

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 v4.3

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
MutationTaster	Benign	1.0	P;P
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

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: rs176036; hg19: chrX-140993264; COSMIC: COSV53572823;