Variant X-141905540-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005462.5(MAGEC1):c.136G>A(p.Asp46Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,097,901 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000016 ( 0 hom. 7 hem. )

Consequence

MAGEC1
NM_005462.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.38

Variant links:

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]

MAGEC1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.070494175).

BS2

High Hemizygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGEC1	NM_005462.5 linkuse as main transcript	c.136G>A	p.Asp46Asn	missense_variant	4/4	ENST00000285879.5
MAGEC1	XM_011531418.3 linkuse as main transcript	c.136G>A	p.Asp46Asn	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGEC1	ENST00000285879.5 linkuse as main transcript	c.136G>A	p.Asp46Asn	missense_variant	4/4	1	NM_005462.5	P3	O60732-1
MAGEC1	ENST00000406005.2 linkuse as main transcript	c.-122G>A		5_prime_UTR_variant	3/4	1		A2	O60732-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183267

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67753

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000134

Gnomad EAS exome

AF:

0.0000722

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1097901

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

363405

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000310

Gnomad4 EAS exome

AF:

0.0000332

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000131

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 17, 2024

The c.136G>A (p.D46N) alteration is located in exon 4 (coding exon 2) of the MAGEC1 gene. This alteration results from a G to A substitution at nucleotide position 136, causing the aspartic acid (D) at amino acid position 46 to be replaced by an asparagine (N). 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

0.12

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-1.1

CADD

Benign

7.1

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0042

FATHMM_MKL

Benign

0.0051

LIST_S2

Benign

0.28

M_CAP

Benign

0.0013

MetaRNN

Benign

0.070

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.12

REVEL

Benign

0.10

Sift

Pathogenic

0.0

Sift4G

Benign

0.065

Polyphen

0.96

Vest4

0.036

MutPred

0.12

Loss of phosphorylation at Y49 (P = 0.1069);

MVP

0.048

ClinPred

0.075

GERP RS

0.13

Varity_R

0.066

gMVP

0.017

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over