Variant chrX-141881576-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_138702.1(MAGEC3):c.689G>C(p.Arg230Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000456 in 1,097,438 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 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 ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000046 ( 0 hom. 2 hem. )

Consequence

MAGEC3
NM_138702.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.504

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14344567).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEC3	NM_138702.1 linkuse as main transcript	c.689G>C	p.Arg230Pro	missense_variant	4/8	ENST00000298296.1	NP_619647.1	Q8TD91-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEC3	ENST00000298296.1 linkuse as main transcript	c.689G>C	p.Arg230Pro	missense_variant	4/8	1	NM_138702.1	ENSP00000298296.1		Q8TD91-1
MAGEC3	ENST00000443323.2 linkuse as main transcript	c.-119+973G>C		intron_variant		1		ENSP00000438254.1		Q3SYA6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000547

AC:

AN:

182674

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67162

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:

0.00

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.00000456

AC:

AN:

1097438

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

362814

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:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2023

The c.689G>C (p.R230P) alteration is located in exon 4 (coding exon 4) of the MAGEC3 gene. This alteration results from a G to C substitution at nucleotide position 689, causing the arginine (R) at amino acid position 230 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

5.3

DANN

Benign

0.90

DEOGEN2

Benign

0.0077

FATHMM_MKL

Benign

0.0070

LIST_S2

Benign

0.097

M_CAP

Benign

0.010

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

PrimateAI

Benign

0.34

PROVEAN

Benign

1.3

REVEL

Benign

0.083

Sift

Uncertain

0.020

Sift4G

Pathogenic

0.0

Polyphen

0.054

Vest4

0.19

MutPred

0.69

Gain of catalytic residue at R230 (P = 0.0458);

MVP

0.10

MPC

0.12

ClinPred

0.074

GERP RS

-4.1

Varity_R

0.18

gMVP

0.70

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over