X-141906093-A-G

Position:

• chrX-141906093-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005462.5(MAGEC1):​c.689A>G​(p.Gln230Arg) 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. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 26)
• Consequence: MAGEC1 NM_005462.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.915

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06550211).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEC1	NM_005462.5	c.689A>G	p.Gln230Arg	missense_variant	4/4	ENST00000285879.5	NP_005453.2
MAGEC1	XM_011531418.3	c.689A>G	p.Gln230Arg	missense_variant	4/4		XP_011529720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEC1	ENST00000285879.5	c.689A>G	p.Gln230Arg	missense_variant	4/4	1	NM_005462.5	ENSP00000285879	P3
MAGEC1	ENST00000406005.2	c.-115+546A>G		intron_variant		1		ENSP00000385500	A2

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 26

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.689A>G (p.Q230R) alteration is located in exon 4 (coding exon 2) of the MAGEC1 gene. This alteration results from a A to G substitution at nucleotide position 689, causing the glutamine (Q) at amino acid position 230 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	11
DANN	Benign	0.19
DEOGEN2	Benign	0.0058	T
FATHMM_MKL	Benign	0.0070	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.041
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.71	T
Polyphen		0.0040	B
Vest4		0.059
MutPred		0.14		Gain of phosphorylation at S231 (P = 0.1146);
MVP		0.055
ClinPred		0.18	T
Varity_R		0.15
gMVP		0.0095

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: rs1397011686; hg19: chrX-140993879;