rs747108314

Variant names:

• chrX-141905993-C-G
• rs747108314
• NM_005462.5:c.589C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-141905993-C-G
• chrX-141905993-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005462.5(MAGEC1):​c.589C>G​(p.Pro197Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P197P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000088 (0 hom., 0 hem., cov: 34)
  • Exomes 𝑓: 0.0000027 (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: -0.0760
• Publications: 1 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05077201).

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.589C>G	p.Pro197Ala	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.589C>G	p.Pro197Ala	missense	Exon 4 of 4	ENSP00000285879.4	O60732-1
	MAGEC1	ENST00000406005.2	TSL:1	c.-115+446C>G		intron	N/A	ENSP00000385500.2	O60732-2

Frequencies

GnomAD3 genomes AF: 0.00000882 AC: 1 AN: 113370 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000378

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000547 AC: 1 AN: 182941 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000274 AC: 3 AN: 1093023 Hom.: 0 Cov.: 103 AF XY: 0.00 AC XY: 0 AN XY: 361993

⚠️ 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: 25942

American (AMR) AF: 0.00 AC: 0 AN: 34933

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19233

East Asian (EAS) AF: 0.00 AC: 0 AN: 30006

South Asian (SAS) AF: 0.00 AC: 0 AN: 53627

European-Finnish (FIN) AF: 0.0000253 AC: 1 AN: 39594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4122

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 839823

Other (OTH) AF: 0.0000219 AC: 1 AN: 45743

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000102688), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000882 AC: 1 AN: 113370 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 35782

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

African (AFR) AF: 0.00 AC: 0 AN: 31267

American (AMR) AF: 0.00 AC: 0 AN: 10807

Ashkenazi Jewish (ASJ) AF: 0.000378 AC: 1 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3610

South Asian (SAS) AF: 0.00 AC: 0 AN: 2833

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53432

Other (OTH) AF: 0.00 AC: 0 AN: 1537

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000827 AC: 1

ClinVar

ClinVar submissions

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	Benign	0.16
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.9
DANN	Benign	0.52
DEOGEN2	Benign	0.0057	T
FATHMM_MKL	Benign	0.0083	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.97	L
PhyloP100		-0.076
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.035
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.027	D
Polyphen		0.012	B
Vest4		0.11
MVP		0.048
ClinPred		0.068	T
Varity_R		0.059
gMVP		0.011
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: rs747108314; hg19: chrX-140993779; COSMIC: COSV107256963;