Genetic Variant NM_005462.5:c.283C>T (chrX-141905687-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005462.5(MAGEC1):c.283C>T(p.Pro95Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,874 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P95T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

MAGEC1
NM_005462.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.298

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11278102).

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.283C>T	p.Pro95Ser	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.283C>T	p.Pro95Ser	missense	Exon 4 of 4	ENSP00000285879.4	O60732-1
	MAGEC1	ENST00000406005.2	TSL:1	c.-115+140C>T		intron	N/A	ENSP00000385500.2	O60732-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1097874

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363492

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26400

American (AMR)

AF:

0.00

AC:

AN:

35192

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19383

East Asian (EAS)

AF:

0.00

AC:

AN:

30205

South Asian (SAS)

AF:

0.00

AC:

AN:

54146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40531

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

841794

Other (OTH)

AF:

0.00

AC:

AN:

46088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.91

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0053

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.29

M_CAP

Benign

0.035

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.70

MutationAssessor

Benign

0.34

PhyloP100

-0.30

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.72

REVEL

Benign

0.042

Sift

Pathogenic

0.0

Sift4G

Benign

0.32

Polyphen

0.90

Vest4

0.083

MutPred

0.25

Gain of phosphorylation at P95 (P = 0.0064)

MVP

0.048

ClinPred

0.25

Varity_R

0.087

gMVP

0.041

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over