Genetic Variant NM_016249.4:c.557G>A (chrX-142203431-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_016249.4(MAGEC2):c.557G>A(p.Arg186His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,209,560 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 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. R186L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 3 hem., cov: 22)

Exomes 𝑓: 0.000012 ( 0 hom. 2 hem. )

Consequence

MAGEC2
NM_016249.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.102

Publications

3 publications found

Variant links:

Genes affected

MAGEC2 (HGNC:13574): (MAGE family member C2) This gene is a member of the MAGEC gene family. It is not expressed in normal tissues, except for testis, and is expressed in tumors of various histological types. This gene and the other MAGEC genes are clustered on chromosome Xq26-q27. [provided by RefSeq, Oct 2009]

MAGEC2 links:

ENSG00000288098 (HGNC:):

ENSG00000288098 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07703677).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016249.4. 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
	MAGEC2	NM_016249.4	MANE Select	c.557G>A	p.Arg186His	missense	Exon 3 of 3	NP_057333.1	Q9UBF1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAGEC2	ENST00000247452.4	TSL:1 MANE Select	c.557G>A	p.Arg186His	missense	Exon 3 of 3	ENSP00000354660.2	Q9UBF1
ENSG00000288098	ENST00000664519.1		n.300+7647C>T		intron	N/A
ENSG00000288098	ENST00000842232.1		n.78+7647C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000537

AC:

AN:

111663

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000942

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:

0.0000218

AC:

AN:

183339

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.0000729

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000118

AC:

AN:

1097897

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

363259

show subpopulations

African (AFR)

AF:

0.000189

AC:

AN:

26394

American (AMR)

AF:

0.0000852

AC:

AN:

35206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19385

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30204

South Asian (SAS)

AF:

0.00

AC:

AN:

54138

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40523

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

841827

Other (OTH)

AF:

0.0000434

AC:

AN:

46085

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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

AF:

0.0000537

AC:

AN:

111663

Hom.:

Cov.:

AF XY:

0.0000886

AC XY:

AN XY:

33851

show subpopulations

African (AFR)

AF:

0.000163

AC:

AN:

30663

American (AMR)

AF:

0.0000942

AC:

AN:

10618

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2638

East Asian (EAS)

AF:

0.00

AC:

AN:

3503

South Asian (SAS)

AF:

0.00

AC:

AN:

2611

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6114

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53088

Other (OTH)

AF:

0.00

AC:

AN:

1502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.8

(source)

DANN

Benign

0.38

DEOGEN2

Benign

0.041

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.052

M_CAP

Benign

0.0022

MetaRNN

Benign

0.077

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.74

PhyloP100

-0.10

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.35

REVEL

Benign

0.027

Sift

Benign

0.23

Sift4G

Benign

0.44

Polyphen

0.022

Vest4

0.11

MutPred

0.67

Loss of MoRF binding (P = 0.0933)

MVP

0.10

MPC

0.0099

ClinPred

0.011

GERP RS

-0.088

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.026

gMVP

0.20

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over