Genetic Variant MAGEC3:p.Leu320Leu (chrX-141895317-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_138702.1(MAGEC3):c.958C>T(p.Leu320Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,207,295 control chromosomes in the GnomAD database, including 29,650 homozygotes. There are 97,156 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 3870 hom., 8435 hem., cov: 21)

Exomes 𝑓: 0.25 ( 25780 hom. 88721 hem. )

Consequence

MAGEC3
NM_138702.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.18

Publications

5 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.04).

BP7

Synonymous conserved (PhyloP=-2.18 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEC3	NM_138702.1 link	c.958C>T	p.Leu320Leu	synonymous_variant	Exon 5 of 8	ENST00000298296.1	NP_619647.1	Q8TD91-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGEC3	ENST00000298296.1 link	c.958C>T	p.Leu320Leu	synonymous_variant	Exon 5 of 8	1	NM_138702.1	ENSP00000298296.1		Q8TD91-1

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

31594

AN:

109437

Hom.:

3870

Cov.:

show subpopulations

Gnomad AFR

AF:

0.435

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.312

Gnomad EAS

AF:

0.0484

Gnomad SAS

AF:

0.0783

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.312

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.281

GnomAD2 exomes

AF:

0.222

AC:

40612

AN:

183234

AF XY:

0.213

show subpopulations

Gnomad AFR exome

AF:

0.452

Gnomad AMR exome

AF:

0.153

Gnomad ASJ exome

AF:

0.328

Gnomad EAS exome

AF:

0.0511

Gnomad FIN exome

AF:

0.200

Gnomad NFE exome

AF:

0.262

Gnomad OTH exome

AF:

0.243

GnomAD4 exome

AF:

0.252

AC:

276128

AN:

1097814

Hom.:

25780

Cov.:

AF XY:

0.244

AC XY:

88721

AN XY:

363238

show subpopulations

African (AFR)

AF:

0.446

AC:

11759

AN:

26372

American (AMR)

AF:

0.162

AC:

5704

AN:

35185

Ashkenazi Jewish (ASJ)

AF:

0.324

AC:

6270

AN:

19367

East Asian (EAS)

AF:

0.0446

AC:

1347

AN:

30203

South Asian (SAS)

AF:

0.0908

AC:

4917

AN:

54129

European-Finnish (FIN)

AF:

0.201

AC:

8129

AN:

40513

Middle Eastern (MID)

AF:

0.243

AC:

1003

AN:

4133

European-Non Finnish (NFE)

AF:

0.268

AC:

225210

AN:

841843

Other (OTH)

AF:

0.256

AC:

11789

AN:

46069

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

7977

15953

23930

31906

39883

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7998

15996

23994

31992

39990

<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:

0.289

AC:

31605

AN:

109481

Hom.:

3870

Cov.:

AF XY:

0.265

AC XY:

8435

AN XY:

31859

show subpopulations

African (AFR)

AF:

0.435

AC:

12981

AN:

29844

American (AMR)

AF:

0.212

AC:

2193

AN:

10364

Ashkenazi Jewish (ASJ)

AF:

0.312

AC:

816

AN:

2618

East Asian (EAS)

AF:

0.0483

AC:

165

AN:

3417

South Asian (SAS)

AF:

0.0778

AC:

198

AN:

2545

European-Finnish (FIN)

AF:

0.190

AC:

1113

AN:

5867

Middle Eastern (MID)

AF:

0.310

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.258

AC:

13557

AN:

52453

Other (OTH)

AF:

0.277

AC:

412

AN:

1487

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

791

1583

2374

3166

3957

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

304

608

912

1216

1520

<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:

0.274

Hom.:

2525

Bravo

AF:

0.302

EpiCase

AF:

0.268

EpiControl

AF:

0.264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.35

(source)

DANN

Benign

0.49

PhyloP100

-2.2

Mutation Taster

=290/10

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over