rs176037

Variant names:

• chrX-141905856-C-G
• rs176037
• NM_005462.5:c.452C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-141905856-C-G
• chrX-141905856-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.452C>G​(p.Thr151Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000037 (0 hom. 2 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAGEC1 NM_005462.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.627
• Publications: 24 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=0.010836571).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEC1	NM_005462.5	MANE Select	c.452C>G	p.Thr151Ser	missense	Exon 4 of 4	NP_005453.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEC1	ENST00000285879.5	TSL:1 MANE Select	c.452C>G	p.Thr151Ser	missense	Exon 4 of 4	ENSP00000285879.4
	MAGEC1	ENST00000406005.2	TSL:1	c.-115+309C>G		intron	N/A	ENSP00000385500.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 110064 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

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: 0.00000620 AC: 1 AN: 161287 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: 0.0000140

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000368 AC: 4 AN: 1087465 Hom.: 0 Cov.: 52 AF XY: 0.00000553 AC XY: 2 AN XY: 361561

⚠️ 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: 25931

American (AMR) AF: 0.00 AC: 0 AN: 34876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19228

East Asian (EAS) AF: 0.0000334 AC: 1 AN: 29953

South Asian (SAS) AF: 0.0000188 AC: 1 AN: 53221

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39953

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4091

European-Non Finnish (NFE) AF: 0.00000240 AC: 2 AN: 834787

Other (OTH) AF: 0.00 AC: 0 AN: 45425

⚠️ 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 110116 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 32912

African (AFR) AF: 0.00 AC: 0 AN: 30359

American (AMR) AF: 0.00 AC: 0 AN: 10484

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2617

East Asian (EAS) AF: 0.00 AC: 0 AN: 3473

South Asian (SAS) AF: 0.00 AC: 0 AN: 2582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5835

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 215

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52356

Other (OTH) AF: 0.00 AC: 0 AN: 1522

Alfa AF: 0.00 Hom.: 367

ExAC AF: 0.00217 AC: 261

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.38
DANN	Benign	0.23
DEOGEN2	Benign	0.0029	T
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.63
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.044
Sift	Benign	0.48	T
Sift4G	Benign	1.0	T
Polyphen		0.34	B
Vest4		0.048
MutPred		0.15		Loss of glycosylation at T151 (P = 0.0291)
MVP		0.055
ClinPred		0.031	T
Varity_R		0.072
gMVP		0.015
Mutation Taster		=100/0	polymorphism (auto)

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: rs176037; hg19: chrX-140993642;