X-141906805-C-G

Variant names:

• chrX-141906805-C-G
• rs176048
• NM_005462.5:c.1401C>G

Variant summary

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

The NM_005462.5(MAGEC1):​c.1401C>G​(p.His467Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,194,297 control chromosomes in the GnomAD database, including 24,980 homozygotes. There are 88,851 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 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 0.21 (1882 hom., 5096 hem., cov: 21)
  • Exomes 𝑓: 0.24 (23098 hom. 83755 hem.)
• Consequence: MAGEC1 NM_005462.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.303
• Publications: 8 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=0.005238831).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEC1	NM_005462.5	MANE Select	c.1401C>G	p.His467Gln	missense	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.1401C>G	p.His467Gln	missense	Exon 4 of 4	ENSP00000285879.4	O60732-1
	MAGEC1	ENST00000406005.2	TSL:1	c.-115+1258C>G		intron	N/A	ENSP00000385500.2	O60732-2

Frequencies

GnomAD3 genomes AF: 0.213 AC: 21598 AN: 101248 Hom.: 1883 Cov.: 21

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.00362

Gnomad SAS AF: 0.0633

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.193

GnomAD2 exomes AF: 0.182 AC: 33137 AN: 181674 AF XY: 0.183

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.0991

Gnomad ASJ exome AF: 0.253

Gnomad EAS exome AF: 0.00355

Gnomad FIN exome AF: 0.197

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.204

GnomAD4 exome AF: 0.239 AC: 260956 AN: 1092999 Hom.: 23098 Cov.: 54 AF XY: 0.232 AC XY: 83755 AN XY: 360471

African (AFR) AF: 0.178 AC: 4648 AN: 26165

American (AMR) AF: 0.106 AC: 3710 AN: 35077

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 4871 AN: 19199

East Asian (EAS) AF: 0.00173 AC: 52 AN: 30097

South Asian (SAS) AF: 0.0741 AC: 3952 AN: 53301

European-Finnish (FIN) AF: 0.199 AC: 8059 AN: 40453

Middle Eastern (MID) AF: 0.202 AC: 823 AN: 4066

European-Non Finnish (NFE) AF: 0.268 AC: 224526 AN: 838853

Other (OTH) AF: 0.225 AC: 10315 AN: 45788

GnomAD4 genome AF: 0.213 AC: 21587 AN: 101298 Hom.: 1882 Cov.: 21 AF XY: 0.188 AC XY: 5096 AN XY: 27120

African (AFR) AF: 0.190 AC: 5142 AN: 27122

American (AMR) AF: 0.156 AC: 1503 AN: 9611

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 627 AN: 2479

East Asian (EAS) AF: 0.00363 AC: 11 AN: 3034

South Asian (SAS) AF: 0.0618 AC: 128 AN: 2072

European-Finnish (FIN) AF: 0.178 AC: 904 AN: 5069

Middle Eastern (MID) AF: 0.280 AC: 44 AN: 157

European-Non Finnish (NFE) AF: 0.257 AC: 12776 AN: 49766

Other (OTH) AF: 0.190 AC: 261 AN: 1373

Alfa AF: 0.146 Hom.: 997

Bravo AF: 0.207

TwinsUK AF: 0.261 AC: 967

ALSPAC AF: 0.256 AC: 740

ESP6500AA AF: 0.195 AC: 749

ESP6500EA AF: 0.253 AC: 1702

ExAC AF: 0.188 AC: 22770

EpiCase AF: 0.258

EpiControl AF: 0.253

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-1.1	T
BayesDel_noAF	Benign	-1.2
CADD	Benign	0.0030
DANN	Benign	0.25
DEOGEN2	Benign	0.0013	T
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.90	N
PhyloP100		-0.30
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.071
Sift	Benign	0.47	T
Sift4G	Benign	0.11	T
Polyphen		0.0010	B
Vest4		0.013
MutPred		0.14		Gain of solvent accessibility (P = 0.0837)
ClinPred		0.00087	T
Varity_R		0.082
gMVP		0.0094
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: rs176048; hg19: chrX-140994591; COSMIC: COSV53572337;