rs763589156

Variant names:

• chrX-141906014-C-A
• rs763589156
• NM_005462.5:c.610C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-141906014-C-A
• chrX-141906014-C-G
• chrX-141906014-C-T

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.610C>A​(p.Arg204Ser) 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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R204C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000055 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAGEC1 NM_005462.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• 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=0.08332339).

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.610C>A	p.Arg204Ser	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.610C>A	p.Arg204Ser	missense	Exon 4 of 4	ENSP00000285879.4	O60732-1
	MAGEC1	ENST00000406005.2	TSL:1	c.-115+467C>A		intron	N/A	ENSP00000385500.2	O60732-2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000548 AC: 6 AN: 1094066 Hom.: 0 Cov.: 108 AF XY: 0.00 AC XY: 0 AN XY: 361502

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26289

American (AMR) AF: 0.0000286 AC: 1 AN: 34935

Ashkenazi Jewish (ASJ) AF: 0.0000520 AC: 1 AN: 19214

East Asian (EAS) AF: 0.00 AC: 0 AN: 30048

South Asian (SAS) AF: 0.00 AC: 0 AN: 53922

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40453

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4121

European-Non Finnish (NFE) AF: 0.00000477 AC: 4 AN: 839227

Other (OTH) AF: 0.00 AC: 0 AN: 45857

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.072
DANN	Benign	0.30
DEOGEN2	Benign	0.0015	T
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.14
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.057
Sift	Benign	0.20	T
Sift4G	Benign	1.0	T
Polyphen		0.80	P
Vest4		0.12
MutPred		0.25		Loss of sheet (P = 0.0315)
MVP		0.055
ClinPred		0.32	T
Varity_R		0.17
gMVP		0.013
Mutation Taster		=99/1	polymorphism

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: rs763589156; hg19: chrX-140993800;