chrX-141905802-G-A

Variant names:

• chrX-141905802-G-A
• rs2018180078
• NM_005462.5:c.398G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005462.5(MAGEC1):​c.398G>A​(p.Ser133Asn) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: MAGEC1 NM_005462.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.297
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093379915).

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.398G>A	p.Ser133Asn	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.398G>A	p.Ser133Asn	missense	Exon 4 of 4	ENSP00000285879.4	O60732-1
	MAGEC1	ENST00000406005.2	TSL:1	c.-115+255G>A		intron	N/A	ENSP00000385500.2	O60732-2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.92
CADD	Benign	9.9
DANN	Benign	0.47
DEOGEN2	Benign	0.0036	T
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.30
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.043
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.065	T
Polyphen		0.034	B
Vest4		0.18
MVP		0.048
ClinPred		0.10	T
Varity_R		0.21
gMVP		0.012
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2018180078; hg19: chrX-140993588; COSMIC: COSV99595773;