dbSNP rs759399130: MAGEC3:p.Arg43Gln (chrX-141865475-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_138702.1(MAGEC3):c.128G>A(p.Arg43Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,205,417 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 40 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. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R43L) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.00013 ( 0 hom. 40 hem. )

Consequence

MAGEC3
NM_138702.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.257

Publications

2 publications found

Variant links:

Genes affected

MAGEC3 (HGNC:23798): (MAGE family member C3) This gene is a member of the MAGEC gene family. The members of this family are not expressed in normal tissues, except for testis, and are expressed in tumors of various histological types. The MAGEC genes are clustered on chromosome Xq26-q27. Two transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MAGEC3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04527691).

BP6

Variant X-141865475-G-A is Benign according to our data. Variant chrX-141865475-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2349463.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 40 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138702.1. 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
	MAGEC3	NM_138702.1	MANE Select	c.128G>A	p.Arg43Gln	missense	Exon 2 of 8	NP_619647.1	Q8TD91-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEC3	ENST00000298296.1	TSL:1 MANE Select	c.128G>A	p.Arg43Gln	missense	Exon 2 of 8	ENSP00000298296.1	Q8TD91-1

Frequencies

GnomAD3 genomes

AF:

0.0000540

AC:

AN:

111065

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000943

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000336

AC:

AN:

178736

AF XY:

0.0000315

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000742

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000626

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000132

AC:

144

AN:

1094304

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

360054

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26339

American (AMR)

AF:

0.00

AC:

AN:

35059

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19228

East Asian (EAS)

AF:

0.0000997

AC:

AN:

30082

South Asian (SAS)

AF:

0.0000375

AC:

AN:

53336

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4087

European-Non Finnish (NFE)

AF:

0.000162

AC:

136

AN:

839909

Other (OTH)

AF:

0.0000654

AC:

AN:

45888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000540

AC:

AN:

111113

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33337

show subpopulations

African (AFR)

AF:

0.0000327

AC:

AN:

30540

American (AMR)

AF:

0.00

AC:

AN:

10465

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2634

East Asian (EAS)

AF:

0.00

AC:

AN:

3513

South Asian (SAS)

AF:

0.00

AC:

AN:

2599

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.0000943

AC:

AN:

53008

Other (OTH)

AF:

0.00

AC:

AN:

1508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

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:

0.000142

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.36

(source)

DANN

Benign

0.10

DEOGEN2

Benign

0.0038

FATHMM_MKL

Benign

0.000090

LIST_S2

Benign

0.32

M_CAP

Benign

0.0038

MetaRNN

Benign

0.045

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

PhyloP100

-0.26

PrimateAI

Benign

0.28

PROVEAN

Benign

0.48

REVEL

Benign

0.012

Sift

Benign

1.0

Sift4G

Benign

0.77

Polyphen

0.0010

Vest4

0.11

MVP

0.15

MPC

0.021

ClinPred

0.0058

GERP RS

0.12

Varity_R

0.027

gMVP

0.0077

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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