X-141905478-G-C

Position:

• chrX-141905478-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005462.5(MAGEC1):​c.74G>C​(p.Cys25Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C25Y) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 23)
• 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046875566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEC1	NM_005462.5	c.74G>C	p.Cys25Ser	missense_variant	4/4	ENST00000285879.5	NP_005453.2
MAGEC1	XM_011531418.3	c.74G>C	p.Cys25Ser	missense_variant	4/4		XP_011529720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEC1	ENST00000285879.5	c.74G>C	p.Cys25Ser	missense_variant	4/4	1	NM_005462.5	ENSP00000285879.4
MAGEC1	ENST00000406005	c.-184G>C		5_prime_UTR_variant	3/4	1		ENSP00000385500.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.010
DANN	Benign	0.38
DEOGEN2	Benign	0.0030	T
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.034
Sift	Benign	0.56	T
Sift4G	Benign	0.79	T
Polyphen		0.62	P
Vest4		0.081
MutPred		0.24		Gain of phosphorylation at C25 (P = 4e-04);
MVP		0.030
ClinPred		0.12	T
GERP RS		-0.30
Varity_R		0.045
gMVP		0.010

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;