chrX-141906731-C-G

Variant names:

• chrX-141906731-C-G
• rs62611966
• NM_005462.5:c.1327C>G

Variant summary

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

The ENST00000285879.5(MAGEC1):​c.1327C>G​(p.Leu443Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0981 in 1,201,732 control chromosomes in the GnomAD database, including 4,875 homozygotes. There are 38,258 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 0.078 (342 hom., 2197 hem., cov: 22)
  • Exomes 𝑓: 0.10 (4533 hom. 36061 hem.)
• Consequence: MAGEC1 ENST00000285879.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104
• Publications: 7 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=0.0017526746).
• 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: ENST00000285879.5. 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.1327C>G	p.Leu443Val	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.1327C>G	p.Leu443Val	missense	Exon 4 of 4	ENSP00000285879.4
	MAGEC1	ENST00000406005.2	TSL:1	c.-115+1184C>G		intron	N/A	ENSP00000385500.2

Frequencies

GnomAD3 genomes AF: 0.0783 AC: 8561 AN: 109404 Hom.: 344 Cov.: 22

Gnomad AFR AF: 0.0520

Gnomad AMI AF: 0.0295

Gnomad AMR AF: 0.0632

Gnomad ASJ AF: 0.0356

Gnomad EAS AF: 0.0450

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0826

Gnomad MID AF: 0.0455

Gnomad NFE AF: 0.0984

Gnomad OTH AF: 0.0753

GnomAD2 exomes AF: 0.0905 AC: 16471 AN: 182070 AF XY: 0.0945

Gnomad AFR exome AF: 0.0500

Gnomad AMR exome AF: 0.0899

Gnomad ASJ exome AF: 0.0417

Gnomad EAS exome AF: 0.0457

Gnomad FIN exome AF: 0.0917

Gnomad NFE exome AF: 0.0987

Gnomad OTH exome AF: 0.0820

GnomAD4 exome AF: 0.100 AC: 109294 AN: 1092286 Hom.: 4533 Cov.: 60 AF XY: 0.101 AC XY: 36061 AN XY: 358682

African (AFR) AF: 0.0620 AC: 1615 AN: 26046

American (AMR) AF: 0.0890 AC: 3122 AN: 35090

Ashkenazi Jewish (ASJ) AF: 0.0414 AC: 793 AN: 19168

East Asian (EAS) AF: 0.0474 AC: 1430 AN: 30165

South Asian (SAS) AF: 0.137 AC: 7338 AN: 53649

European-Finnish (FIN) AF: 0.0928 AC: 3750 AN: 40415

Middle Eastern (MID) AF: 0.106 AC: 435 AN: 4085

European-Non Finnish (NFE) AF: 0.104 AC: 86736 AN: 837813

Other (OTH) AF: 0.0889 AC: 4075 AN: 45855

GnomAD4 genome AF: 0.0782 AC: 8556 AN: 109446 Hom.: 342 Cov.: 22 AF XY: 0.0681 AC XY: 2197 AN XY: 32264

African (AFR) AF: 0.0520 AC: 1543 AN: 29666

American (AMR) AF: 0.0629 AC: 661 AN: 10513

Ashkenazi Jewish (ASJ) AF: 0.0356 AC: 93 AN: 2616

East Asian (EAS) AF: 0.0452 AC: 155 AN: 3433

South Asian (SAS) AF: 0.126 AC: 312 AN: 2483

European-Finnish (FIN) AF: 0.0826 AC: 491 AN: 5944

Middle Eastern (MID) AF: 0.0450 AC: 9 AN: 200

European-Non Finnish (NFE) AF: 0.0985 AC: 5161 AN: 52418

Other (OTH) AF: 0.0743 AC: 111 AN: 1494

Alfa AF: 0.0517 Hom.: 402

Bravo AF: 0.0765

TwinsUK AF: 0.100 AC: 371

ALSPAC AF: 0.100 AC: 290

ESP6500AA AF: 0.0511 AC: 196

ESP6500EA AF: 0.0994 AC: 668

ExAC AF: 0.0926 AC: 11190

EpiCase AF: 0.0920

EpiControl AF: 0.0963

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.95	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	10
DANN	Benign	0.34
DEOGEN2	Benign	0.0058	T
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.10
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.072
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.24	T
Polyphen		0.89	P
Vest4		0.016
ClinPred		0.0077	T
GERP RS		0.13
Varity_R		0.12
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: rs62611966; hg19: chrX-140994517;