Genetic Variant NM_138702.1:c.475G>A (chrX-141879391-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.475G>A(p.Val159Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000523 in 1,185,519 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 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 0.00015 ( 0 hom., 6 hem., cov: 22)

Exomes 𝑓: 0.000042 ( 0 hom. 11 hem. )

Consequence

MAGEC3
NM_138702.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.264

Publications

1 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=0.02492258).

BP6

Variant X-141879391-G-A is Benign according to our data. Variant chrX-141879391-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2661552.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 6 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.475G>A	p.Val159Ile	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.475G>A	p.Val159Ile	missense	Exon 3 of 8	ENSP00000298296.1	Q8TD91-1

Frequencies

GnomAD3 genomes

AF:

0.000155

AC:

AN:

109811

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000334

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00106

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:

0.0000950

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000134

AC:

AN:

141905

AF XY:

0.000140

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000700

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000337

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000418

AC:

AN:

1075708

Hom.:

Cov.:

AF XY:

0.0000315

AC XY:

AN XY:

348848

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25909

American (AMR)

AF:

0.000536

AC:

AN:

31709

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18926

East Asian (EAS)

AF:

0.00

AC:

AN:

29254

South Asian (SAS)

AF:

0.0000586

AC:

AN:

51156

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39156

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4102

European-Non Finnish (NFE)

AF:

0.0000301

AC:

AN:

830207

Other (OTH)

AF:

0.00

AC:

AN:

45289

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

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:

0.000155

AC:

AN:

109811

Hom.:

Cov.:

AF XY:

0.000187

AC XY:

AN XY:

32119

show subpopulations

African (AFR)

AF:

0.0000334

AC:

AN:

29969

American (AMR)

AF:

0.00106

AC:

AN:

10378

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2625

East Asian (EAS)

AF:

0.00

AC:

AN:

3430

South Asian (SAS)

AF:

0.00

AC:

AN:

2434

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5966

Middle Eastern (MID)

AF:

0.00

AC:

AN:

235

European-Non Finnish (NFE)

AF:

0.0000950

AC:

AN:

52636

Other (OTH)

AF:

0.00

AC:

AN:

1462

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

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:

0.000151

ExAC

AF:

0.0000422

AC:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-1.1

CADD

Benign

6.3

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0059

FATHMM_MKL

Benign

0.0040

LIST_S2

Benign

0.34

M_CAP

Benign

0.0026

MetaRNN

Benign

0.025

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

PhyloP100

0.26

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.13

REVEL

Benign

0.018

Sift

Uncertain

0.0060

Sift4G

Pathogenic

0.0

Polyphen

0.12

Vest4

0.019

MVP

0.048

MPC

0.024

ClinPred

0.018

GERP RS

-2.3

Varity_R

0.063

gMVP

0.016

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