X-141905814-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_005462.5(MAGEC1):c.410C>G(p.Ser137Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,098,195 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.000027 (0 hom. 11 hem.)
• Consequence: MAGEC1 NM_005462.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.72

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

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17599866).
• BP6: Variant X-141905814-C-G is Benign according to our data. Variant chrX-141905814-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3026261.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGEC1	NM_005462.5	c.410C>G	p.Ser137Cys	missense_variant	4/4	ENST00000285879.5
MAGEC1	XM_011531418.3	c.410C>G	p.Ser137Cys	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGEC1	ENST00000285879.5	c.410C>G	p.Ser137Cys	missense_variant	4/4	1	NM_005462.5	P3
MAGEC1	ENST00000406005.2	c.-115+267C>G		intron_variant		1		A2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.0000273 AC: 5 AN: 183481 Hom.: 0 AF XY: 0.0000442 AC XY: 3 AN XY: 67913

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000610

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000273 AC: 30 AN: 1098195 Hom.: 0 Cov.: 36 AF XY: 0.0000303 AC XY: 11 AN XY: 363559

Gnomad4 AFR exome AF: 0.0000379

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000321

Gnomad4 OTH exome AF: 0.0000434

GnomAD4 genome Cov.: 24

Bravo AF: 0.0000189

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

MAGEC1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.76
Cadd	Benign	15
Dann	Benign	0.54
DEOGEN2	Benign	0.0042	T
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	0.97	L
MutationTaster	Benign	1.0	D;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.048
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.88	P
Vest4		0.27
MutPred		0.38		Loss of phosphorylation at S137 (P = 0.0277);
MVP		0.061
ClinPred		0.14	T
Varity_R		0.12
gMVP		0.017

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

Publications

LitVar

Other links and lift over

dbSNP: rs374380387; hg19: chrX-140993600;