rs56256227

Variant names:

• chrX-141907529-C-T
• rs56256227
• NM_005462.5:c.2125C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_005462.5(MAGEC1):​c.2125C>T​(p.His709Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.099 in 1,198,380 control chromosomes in the GnomAD database, including 4,117 homozygotes. There are 38,696 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/22 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 0.086 (319 hom., 2363 hem., cov: 21)
  • Exomes 𝑓: 0.10 (3798 hom. 36333 hem.)
• Consequence: MAGEC1 NM_005462.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.40
• Publications: 9 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.114 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.2125C>T	p.His709Tyr	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.2125C>T	p.His709Tyr	missense	Exon 4 of 4	ENSP00000285879.4	O60732-1
	MAGEC1	ENST00000406005.2	TSL:1	c.-114-561C>T		intron	N/A	ENSP00000385500.2	O60732-2

Frequencies

GnomAD3 genomes AF: 0.0861 AC: 9160 AN: 106388 Hom.: 320 Cov.: 21

Gnomad AFR AF: 0.0711

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0685

Gnomad ASJ AF: 0.0341

Gnomad EAS AF: 0.0485

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0871

Gnomad MID AF: 0.0644

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0873

GnomAD2 exomes AF: 0.0912 AC: 16309 AN: 178747 AF XY: 0.0944

Gnomad AFR exome AF: 0.0687

Gnomad AMR exome AF: 0.0901

Gnomad ASJ exome AF: 0.0396

Gnomad EAS exome AF: 0.0460

Gnomad FIN exome AF: 0.0907

Gnomad NFE exome AF: 0.0985

Gnomad OTH exome AF: 0.0829

GnomAD4 exome AF: 0.100 AC: 109480 AN: 1091943 Hom.: 3798 Cov.: 33 AF XY: 0.101 AC XY: 36333 AN XY: 358027

African (AFR) AF: 0.0766 AC: 2004 AN: 26162

American (AMR) AF: 0.0895 AC: 3116 AN: 34820

Ashkenazi Jewish (ASJ) AF: 0.0400 AC: 764 AN: 19111

East Asian (EAS) AF: 0.0468 AC: 1412 AN: 30167

South Asian (SAS) AF: 0.135 AC: 7246 AN: 53667

European-Finnish (FIN) AF: 0.0918 AC: 3715 AN: 40455

Middle Eastern (MID) AF: 0.102 AC: 419 AN: 4105

European-Non Finnish (NFE) AF: 0.104 AC: 86727 AN: 837640

Other (OTH) AF: 0.0890 AC: 4077 AN: 45816

GnomAD4 genome AF: 0.0861 AC: 9159 AN: 106437 Hom.: 319 Cov.: 21 AF XY: 0.0788 AC XY: 2363 AN XY: 30005

African (AFR) AF: 0.0712 AC: 2068 AN: 29026

American (AMR) AF: 0.0681 AC: 690 AN: 10130

Ashkenazi Jewish (ASJ) AF: 0.0341 AC: 88 AN: 2581

East Asian (EAS) AF: 0.0487 AC: 157 AN: 3226

South Asian (SAS) AF: 0.126 AC: 286 AN: 2276

European-Finnish (FIN) AF: 0.0871 AC: 490 AN: 5627

Middle Eastern (MID) AF: 0.0656 AC: 12 AN: 183

European-Non Finnish (NFE) AF: 0.102 AC: 5226 AN: 51317

Other (OTH) AF: 0.0861 AC: 124 AN: 1440

Alfa AF: 0.0908 Hom.: 3601

Bravo AF: 0.0818

TwinsUK AF: 0.100 AC: 371

ALSPAC AF: 0.100 AC: 290

ESP6500AA AF: 0.0686 AC: 263

ESP6500EA AF: 0.0985 AC: 663

ExAC AF: 0.0932 AC: 11314

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-1.1	T
BayesDel_noAF	Benign	-1.2
CADD	Benign	0.18
DANN	Benign	0.48
DEOGEN2	Benign	0.0033	T
FATHMM_MKL	Benign	0.0036	N
LIST_S2	Benign	0.23	T
MetaRNN	Benign	0.0025	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.69	N
PhyloP100		-4.4
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.059
Sift	Benign	0.16	T
Sift4G	Benign	0.23	T
Polyphen		0.0010	B
Vest4		0.020
ClinPred		0.00058	T
GERP RS		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.95
Varity_R		0.043
gMVP		0.011
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: 12

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs56256227; hg19: chrX-140995315;