rs746221752

Variant names:

• chrX-141906005-C-A
• rs746221752
• NM_005462.5:c.601C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005462.5(MAGEC1):​c.601C>A​(p.Pro201Thr) 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: 35)
  • Exomes 𝑓: 0.000045 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAGEC1 NM_005462.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.788
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.066289335).

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.601C>A	p.Pro201Thr	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.601C>A	p.Pro201Thr	missense	Exon 4 of 4	ENSP00000285879.4	O60732-1
	MAGEC1	ENST00000406005.2	TSL:1	c.-115+458C>A		intron	N/A	ENSP00000385500.2	O60732-2

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD2 exomes AF: 0.00000545 AC: 1 AN: 183355 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000447 AC: 49 AN: 1095070 Hom.: 0 Cov.: 108 AF XY: 0.00 AC XY: 0 AN XY: 362492

⚠️ 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: 26291

American (AMR) AF: 0.0000286 AC: 1 AN: 34947

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19245

East Asian (EAS) AF: 0.00 AC: 0 AN: 30063

South Asian (SAS) AF: 0.00 AC: 0 AN: 53979

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40389

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4132

European-Non Finnish (NFE) AF: 0.0000512 AC: 43 AN: 840132

Other (OTH) AF: 0.0000872 AC: 4 AN: 45892

⚠️ 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.: 35

Alfa AF: 0.0000843 Hom.: 0

ExAC AF: 0.0000578 AC: 7

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.42
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.93
CADD	Benign	12
DANN	Benign	0.83
DEOGEN2	Benign	0.0056	T
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.79
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.022
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.0070	B
Vest4		0.096
MVP		0.055
ClinPred		0.16	T
Varity_R		0.11
gMVP		0.035
Mutation Taster		=100/0	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: rs746221752; hg19: chrX-140993791;