Genetic Variant MAGEC2:p.Thr350Thr (chrX-142202938-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_016249.4(MAGEC2):c.1050C>T(p.Thr350Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000406 in 1,209,416 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 158 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., 10 hem., cov: 23)

Exomes 𝑓: 0.00042 ( 0 hom. 148 hem. )

Consequence

MAGEC2
NM_016249.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.147

Variant links:

Genes affected

MAGEC2 (HGNC:13574): (MAGE family member C2) This gene is a member of the MAGEC gene family. It is not expressed in normal tissues, except for testis, and is expressed in tumors of various histological types. This gene and the other MAGEC genes are clustered on chromosome Xq26-q27. [provided by RefSeq, Oct 2009]

MAGEC2 links:

ENSG00000288098 (HGNC:):

ENSG00000288098 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant X-142202938-G-A is Benign according to our data. Variant chrX-142202938-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2661573.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.147 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGEC2	NM_016249.4 link	c.1050C>T	p.Thr350Thr	synonymous_variant	Exon 3 of 3	ENST00000247452.4	NP_057333.1	Q9UBF1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGEC2	ENST00000247452.4 link	c.1050C>T	p.Thr350Thr	synonymous_variant	Exon 3 of 3	1	NM_016249.4	ENSP00000354660.2		Q9UBF1
ENSG00000288098	ENST00000664519.1 link	n.300+7154G>A		intron_variant	Intron 2 of 9

Frequencies

GnomAD3 genomes

AF:

0.000251

AC:

AN:

111592

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

33790

show subpopulations

Gnomad AFR

AF:

0.0000653

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000948

Gnomad ASJ

AF:

0.00302

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000301

Gnomad OTH

AF:

0.000666

GnomAD3 exomes

AF:

0.000458

AC:

AN:

183440

Hom.:

AF XY:

0.000383

AC XY:

AN XY:

67874

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00588

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000464

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000421

AC:

462

AN:

1097774

Hom.:

Cov.:

AF XY:

0.000408

AC XY:

148

AN XY:

363138

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00459

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000399

Gnomad4 OTH exome

AF:

0.000759

GnomAD4 genome

AF:

0.000260

AC:

AN:

111642

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

33850

show subpopulations

Gnomad4 AFR

AF:

0.0000977

Gnomad4 AMR

AF:

0.0000947

Gnomad4 ASJ

AF:

0.00302

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000301

Gnomad4 OTH

AF:

0.000657

Alfa

AF:

0.00139

Hom.:

Bravo

AF:

0.000329

EpiCase

AF:

0.000491

EpiControl

AF:

0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MAGEC2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.92

DANN

Benign

0.37

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