chrX-141906731-C-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005462.5(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. 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.

• Frequency:
  • Genomes: 𝑓 0.078 (342 hom., 2197 hem., cov: 22)
  • Exomes 𝑓: 0.10 (4533 hom. 36061 hem.)
• Consequence: MAGEC1 NM_005462.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104

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=0.0017526746).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEC1	NM_005462.5	c.1327C>G	p.Leu443Val	missense_variant	Exon 4 of 4	ENST00000285879.5	NP_005453.2
MAGEC1	XM_011531418.3	c.1327C>G	p.Leu443Val	missense_variant	Exon 4 of 4		XP_011529720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGEC1	ENST00000285879.5	c.1327C>G	p.Leu443Val	missense_variant	Exon 4 of 4	1	NM_005462.5	ENSP00000285879.4
MAGEC1	ENST00000406005.2	c.-115+1184C>G		intron_variant	Intron 3 of 3	1		ENSP00000385500.2

Frequencies

GnomAD3 genomes AF: 0.0783 AC: 8561 AN: 109404 Hom.: 344 Cov.: 22 AF XY: 0.0681 AC XY: 2192 AN XY: 32210

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

GnomAD3 exomes AF: 0.0905 AC: 16471 AN: 182070 Hom.: 626 AF XY: 0.0945 AC XY: 6328 AN XY: 66928

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 SAS exome AF: 0.136

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

Gnomad4 AFR exome AF: 0.0620

Gnomad4 AMR exome AF: 0.0890

Gnomad4 ASJ exome AF: 0.0414

Gnomad4 EAS exome AF: 0.0474

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.0928

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.0889

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

Gnomad4 AFR AF: 0.0520

Gnomad4 AMR AF: 0.0629

Gnomad4 ASJ AF: 0.0356

Gnomad4 EAS AF: 0.0452

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.0826

Gnomad4 NFE AF: 0.0985

Gnomad4 OTH AF: 0.0743

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 v4.3

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
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

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: rs62611966; hg19: chrX-140994517;