dbSNP rs2017940588: MAGEC3:p.Leu91Pro (chrX-141879188-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_138702.1(MAGEC3):c.272T>C(p.Leu91Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000168 in 1,187,842 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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 0.0000090 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 9.3e-7 ( 0 hom. 0 hem. )

Consequence

MAGEC3
NM_138702.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.37

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05137658).

BP6

Variant X-141879188-T-C is Benign according to our data. Variant chrX-141879188-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2268201.Status of the report is criteria_provided_single_submitter, 1 stars.

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.272T>C	p.Leu91Pro	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.272T>C	p.Leu91Pro	missense	Exon 3 of 8	ENSP00000298296.1	Q8TD91-1

Frequencies

GnomAD3 genomes

AF:

0.00000897

AC:

AN:

111469

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.29e-7

AC:

AN:

1076373

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

347741

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25987

American (AMR)

AF:

0.00

AC:

AN:

33937

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18089

East Asian (EAS)

AF:

0.00

AC:

AN:

29864

South Asian (SAS)

AF:

0.00

AC:

AN:

49934

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39634

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3370

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

830434

Other (OTH)

AF:

0.0000222

AC:

AN:

45124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00000897

AC:

AN:

111469

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33697

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30623

American (AMR)

AF:

0.00

AC:

AN:

10640

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2636

East Asian (EAS)

AF:

0.00

AC:

AN:

3469

South Asian (SAS)

AF:

0.00

AC:

AN:

2605

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6143

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

52933

Other (OTH)

AF:

0.00

AC:

AN:

1499

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

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

0.062

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.82

(source)

DANN

Benign

0.14

DEOGEN2

Benign

0.0042

FATHMM_MKL

Benign

0.00039

LIST_S2

Benign

0.15

M_CAP

Benign

0.0061

MetaRNN

Benign

0.051

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

PhyloP100

-3.4

PrimateAI

Benign

0.28

PROVEAN

Benign

1.3

REVEL

Benign

0.012

Sift

Benign

0.47

Sift4G

Benign

0.11

Polyphen

0.0

Vest4

0.040

MutPred

0.46

Gain of disorder (P = 0.0153)

MVP

0.081

MPC

0.024

ClinPred

0.062

GERP RS

-0.14

Varity_R

0.051

gMVP

0.16

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over