rs182757967

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000358075.11(MAGT1):c.-30G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00066 in 1,204,182 control chromosomes in the GnomAD database, including 2 homozygotes. There are 252 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 0.00049 ( 1 hom., 14 hem., cov: 24)

Exomes 𝑓: 0.00068 ( 1 hom. 238 hem. )

Consequence

MAGT1
ENST00000358075.11 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.04

Variant links:

Genes affected

MAGT1 (HGNC:28880): (magnesium transporter 1) This gene encodes a ubiquitously expressed magnesium cation transporter protein that localizes to the cell membrane. This protein also associates with N-oligosaccharyl transferase and therefore may have a role in N-glycosylation. Mutations in this gene cause a form of X-linked intellectual disability (XLID). This gene may have multiple in-frame translation initiation sites, one of which would encode a shorter protein with an N-terminus containing a signal peptide at amino acids 1-29. [provided by RefSeq, Jul 2017]

MAGT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016403139).

BP6

Variant X-77895440-C-T is Benign according to our data. Variant chrX-77895440-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-77895440-C-T is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd at 14 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGT1	NM_032121.5 linkuse as main transcript	c.67G>A	p.Val23Ile	missense_variant	1/10
MAGT1	NM_001367916.1 linkuse as main transcript			upstream_gene_variant		ENST00000618282.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGT1	ENST00000618282.5 linkuse as main transcript			upstream_gene_variant		1	NM_001367916.1	P1	Q9H0U3-1

Frequencies

GnomAD3 genomes

AF:

0.000488

AC:

AN:

112731

Hom.:

Cov.:

AF XY:

0.000401

AC XY:

AN XY:

34871

show subpopulations

Gnomad AFR

AF:

0.000161

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:

0.00162

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000750

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000677

AC:

114

AN:

168288

Hom.:

AF XY:

0.000599

AC XY:

AN XY:

55108

show subpopulations

Gnomad AFR exome

AF:

0.000165

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:

0.00191

Gnomad NFE exome

AF:

0.00113

Gnomad OTH exome

AF:

0.000236

GnomAD4 exome

AF:

0.000678

AC:

740

AN:

1091398

Hom.:

Cov.:

AF XY:

0.000665

AC XY:

238

AN XY:

357678

show subpopulations

Gnomad4 AFR exome

AF:

0.0000761

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000188

Gnomad4 FIN exome

AF:

0.00219

Gnomad4 NFE exome

AF:

0.000706

Gnomad4 OTH exome

AF:

0.00122

GnomAD4 genome

AF:

0.000488

AC:

AN:

112784

Hom.:

Cov.:

AF XY:

0.000401

AC XY:

AN XY:

34934

show subpopulations

Gnomad4 AFR

AF:

0.000161

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00162

Gnomad4 NFE

AF:

0.000750

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000725

Hom.:

Bravo

AF:

0.000351

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.000991

AC:

120

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 16, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2022	MAGT1: BP4 -

MAGT1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 08, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.78

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.086

T;T

FATHMM_MKL

Benign

0.39

M_CAP

Benign

0.0092

MetaRNN

Benign

0.016

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.070

N;.

REVEL

Benign

0.079

Sift

Benign

0.24

T;.

Sift4G

Benign

0.16

T;T

Vest4

0.28

MVP

0.43

MPC

0.39

ClinPred

0.032

GERP RS

4.6

gMVP

0.15

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