Variant X-141879425-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_138702.1(MAGEC3):c.509C>G(p.Ala170Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,159,966 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 1 hem., cov: 21)

Exomes 𝑓: 0.000022 ( 0 hom. 3 hem. )

Consequence

MAGEC3
NM_138702.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.47

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.025031418).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEC3	NM_138702.1 link	c.509C>G	p.Ala170Gly	missense_variant	3/8	ENST00000298296.1	NP_619647.1	Q8TD91-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGEC3	ENST00000298296.1 link	c.509C>G	p.Ala170Gly	missense_variant	3/8	1	NM_138702.1	ENSP00000298296.1		Q8TD91-1

Frequencies

GnomAD3 genomes

AF:

0.000122

AC:

AN:

106814

Hom.:

Cov.:

AF XY:

0.0000332

AC XY:

AN XY:

30082

show subpopulations

Gnomad AFR

AF:

0.000414

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000997

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000314

AC:

AN:

127516

Hom.:

AF XY:

0.00

AC XY:

AN XY:

37552

show subpopulations

Gnomad AFR exome

AF:

0.000231

Gnomad AMR exome

AF:

0.0000961

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:

0.00

GnomAD4 exome

AF:

0.0000218

AC:

AN:

1053111

Hom.:

Cov.:

AF XY:

0.00000894

AC XY:

AN XY:

335427

show subpopulations

Gnomad4 AFR exome

AF:

0.000550

Gnomad4 AMR exome

AF:

0.000101

Gnomad4 ASJ exome

AF:

0.0000548

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000490

Gnomad4 OTH exome

AF:

0.0000226

GnomAD4 genome

AF:

0.000122

AC:

AN:

106855

Hom.:

Cov.:

AF XY:

0.0000332

AC XY:

AN XY:

30131

show subpopulations

Gnomad4 AFR

AF:

0.000413

Gnomad4 AMR

AF:

0.0000996

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000433

AC:

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

May 09, 2024

The c.509C>G (p.A170G) alteration is located in exon 3 (coding exon 3) of the MAGEC3 gene. This alteration results from a C to G substitution at nucleotide position 509, causing the alanine (A) at amino acid position 170 to be replaced by a glycine (G). 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

Benign

0.11

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.87

DANN

Benign

0.44

DEOGEN2

Benign

0.0044

FATHMM_MKL

Benign

0.0073

LIST_S2

Benign

0.22

M_CAP

Benign

0.0022

MetaRNN

Benign

0.025

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.35

PROVEAN

Benign

0.12

REVEL

Benign

0.023

Sift

Benign

0.054

Sift4G

Benign

0.088

Polyphen

0.19

Vest4

0.038

MVP

0.16

MPC

0.026

ClinPred

0.0092

GERP RS

-1.4

Varity_R

0.078

gMVP

0.013

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