dbSNP rs143001071: MAGEC3:p.Pro108Leu (chrX-141879239-C-T) – 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.323C>T(p.Pro108Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00015 in 1,201,835 control chromosomes in the GnomAD database, including 1 homozygotes. There are 56 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 (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., 5 hem., cov: 22)

Exomes 𝑓: 0.00015 ( 1 hom. 51 hem. )

Consequence

MAGEC3
NM_138702.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.03

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=0.04543066).

BP6

Variant X-141879239-C-T is Benign according to our data. Variant chrX-141879239-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2347769.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 5 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.323C>T	p.Pro108Leu	missense	Exon 3 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.323C>T	p.Pro108Leu	missense	Exon 3 of 8	ENSP00000298296.1	Q8TD91-1

Frequencies

GnomAD3 genomes

AF:

0.000180

AC:

AN:

111199

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:

0.000359

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000132

AC:

AN:

166042

AF XY:

0.000113

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000386

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000773

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000262

Gnomad OTH exome

AF:

0.000239

GnomAD4 exome

AF:

0.000147

AC:

160

AN:

1090636

Hom.:

Cov.:

AF XY:

0.000143

AC XY:

AN XY:

356936

show subpopulations

African (AFR)

AF:

0.000114

AC:

AN:

26298

American (AMR)

AF:

0.0000290

AC:

AN:

34496

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19189

East Asian (EAS)

AF:

0.0000333

AC:

AN:

30016

South Asian (SAS)

AF:

0.00

AC:

AN:

52747

European-Finnish (FIN)

AF:

0.0000498

AC:

AN:

40171

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3984

European-Non Finnish (NFE)

AF:

0.000172

AC:

144

AN:

837923

Other (OTH)

AF:

0.000196

AC:

AN:

45812

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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:

0.000180

AC:

AN:

111199

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

AN XY:

33419

show subpopulations

African (AFR)

AF:

0.0000328

AC:

AN:

30526

American (AMR)

AF:

0.00

AC:

AN:

10553

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2644

East Asian (EAS)

AF:

0.00

AC:

AN:

3484

South Asian (SAS)

AF:

0.00

AC:

AN:

2590

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.000359

AC:

AN:

52935

Other (OTH)

AF:

0.00

AC:

AN:

1481

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000260

Hom.:

Bravo

AF:

0.000155

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.0000907

AC:

ClinVar

ClinVar submissions as Germline

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

0.11

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.043

(source)

DANN

Benign

0.31

DEOGEN2

Benign

0.0096

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.32

M_CAP

Benign

0.0039

MetaRNN

Benign

0.045

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

PhyloP100

-1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.9

REVEL

Benign

0.031

Sift

Pathogenic

0.0

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.077

MVP

0.040

MPC

0.021

ClinPred

0.024

GERP RS

-3.7

Varity_R

0.057

gMVP

0.015

Mutation Taster

=98/2

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