Variant chrX-141881570-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_138702.1(MAGEC3):c.683A>G(p.Lys228Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,209,433 control chromosomes in the GnomAD database, including 20 homozygotes. There are 437 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 7 hom., 177 hem., cov: 23)

Exomes 𝑓: 0.00089 ( 13 hom. 260 hem. )

Consequence

MAGEC3
NM_138702.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0290

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006769985).

BP6

Variant X-141881570-A-G is Benign according to our data. Variant chrX-141881570-A-G is described in ClinVar as [Benign]. Clinvar id is 789873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-141881570-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00605 (677/111857) while in subpopulation AFR AF= 0.0196 (603/30773). AF 95% confidence interval is 0.0183. There are 7 homozygotes in gnomad4. There are 177 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGEC3	NM_138702.1 link	c.683A>G	p.Lys228Arg	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 link	c.683A>G	p.Lys228Arg	missense_variant	4/8	1	NM_138702.1	ENSP00000298296.1		Q8TD91-1
MAGEC3	ENST00000443323.2 link	c.-119+967A>G		intron_variant		1		ENSP00000438254.1		Q3SYA6

Frequencies

GnomAD3 genomes

AF:

0.00604

AC:

675

AN:

111809

Hom.:

Cov.:

AF XY:

0.00515

AC XY:

175

AN XY:

33989

show subpopulations

Gnomad AFR

AF:

0.0196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00537

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.000188

Gnomad OTH

AF:

0.00403

GnomAD3 exomes

AF:

0.00175

AC:

319

AN:

182788

Hom.:

AF XY:

0.00114

AC XY:

AN XY:

67268

show subpopulations

Gnomad AFR exome

AF:

0.0205

Gnomad AMR exome

AF:

0.000768

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:

0.000233

Gnomad OTH exome

AF:

0.00222

GnomAD4 exome

AF:

0.000889

AC:

976

AN:

1097576

Hom.:

Cov.:

AF XY:

0.000716

AC XY:

260

AN XY:

362942

show subpopulations

Gnomad4 AFR exome

AF:

0.0229

Gnomad4 AMR exome

AF:

0.00165

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000925

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000201

Gnomad4 OTH exome

AF:

0.00274

GnomAD4 genome

AF:

0.00605

AC:

677

AN:

111857

Hom.:

Cov.:

AF XY:

0.00520

AC XY:

177

AN XY:

34047

show subpopulations

Gnomad4 AFR

AF:

0.0196

Gnomad4 AMR

AF:

0.00537

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000188

Gnomad4 OTH

AF:

0.00398

Alfa

AF:

0.00119

Hom.:

Bravo

AF:

0.00797

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.0172

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.00199

AC:

242

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000475

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.92

BayesDel_noAF

Benign

-1.1

CADD

Benign

5.9

DANN

Benign

0.90

DEOGEN2

Benign

0.013

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0068

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.85

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-0.24

REVEL

Benign

0.049

Sift

Benign

0.49

Sift4G

Pathogenic

0.0

Polyphen

0.017

Vest4

0.11

MVP

0.10

MPC

0.076

ClinPred

0.00032

GERP RS

-1.8

Varity_R

0.040

gMVP

0.22

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