Genetic Variant MAGEC3:p.Pro223Ser (chrX-141881554-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2

The NM_138702.1(MAGEC3):c.667C>T(p.Pro223Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000479 in 1,209,671 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000051 ( 0 hom. 20 hem. )

Consequence

MAGEC3
NM_138702.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.301

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.39054602).

BP6

Variant X-141881554-C-T is Benign according to our data. Variant chrX-141881554-C-T is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEC3	NM_138702.1 link	c.667C>T	p.Pro223Ser	missense_variant	Exon 4 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.667C>T	p.Pro223Ser	missense_variant	Exon 4 of 8	1	NM_138702.1	ENSP00000298296.1		Q8TD91-1
MAGEC3	ENST00000443323.2 link	c.-119+951C>T		intron_variant	Intron 1 of 2	1		ENSP00000438254.1		Q3SYA6

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111816

Hom.:

Cov.:

AF XY:

0.0000588

AC XY:

AN XY:

34012

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:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000273

AC:

AN:

183036

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67502

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000612

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000510

AC:

AN:

1097855

Hom.:

Cov.:

AF XY:

0.0000551

AC XY:

AN XY:

363213

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000653

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111816

Hom.:

Cov.:

AF XY:

0.0000588

AC XY:

AN XY:

34012

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.85

CADD

Benign

9.1

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0057

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.54

M_CAP

Benign

0.0092

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.4

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.4

REVEL

Benign

0.042

Sift

Benign

0.065

Sift4G

Pathogenic

0.0

Polyphen

0.11

Vest4

0.14

MutPred

0.82

Gain of catalytic residue at P223 (P = 0.0511);

MVP

0.47

MPC

0.14

ClinPred

0.054

GERP RS

0.40

Varity_R

0.043

gMVP

0.29

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over