rs145245774

Variant names:

Variant summary

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

The NM_001367916.1(MAGT1):c.932T>G(p.Val311Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,157,504 control chromosomes in the GnomAD database, including 1 homozygotes. There are 395 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 0.0012 ( 0 hom., 44 hem., cov: 23)

Exomes 𝑓: 0.0011 ( 1 hom. 351 hem. )

Consequence

MAGT1
NM_001367916.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 8.11

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=0.012037069).

BP6

Variant X-77830865-A-C is Benign according to our data. Variant chrX-77830865-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 96213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-77830865-A-C is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 44 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGT1	NM_001367916.1 link	c.932T>G	p.Val311Gly	missense_variant	Exon 9 of 10	ENST00000618282.5	NP_001354845.1
MAGT1	NM_032121.5 link	c.1028T>G	p.Val343Gly	missense_variant	Exon 9 of 10		NP_115497.4	Q9H0U3A0A087WU53

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGT1	ENST00000618282.5 link	c.932T>G	p.Val311Gly	missense_variant	Exon 9 of 10	1	NM_001367916.1	ENSP00000480732.1		Q9H0U3-1

Frequencies

GnomAD3 genomes

AF:

0.00116

AC:

128

AN:

110401

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

33049

show subpopulations

Gnomad AFR

AF:

0.000196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000194

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00742

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00150

Gnomad OTH

AF:

0.000673

GnomAD3 exomes

AF:

0.00153

AC:

260

AN:

169941

Hom.:

AF XY:

0.00154

AC XY:

AN XY:

58395

show subpopulations

Gnomad AFR exome

AF:

0.000335

Gnomad AMR exome

AF:

0.000246

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00922

Gnomad NFE exome

AF:

0.00128

Gnomad OTH exome

AF:

0.00123

GnomAD4 exome

AF:

0.00108

AC:

1136

AN:

1047069

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

351

AN XY:

328835

show subpopulations

Gnomad4 AFR exome

AF:

0.000160

Gnomad4 AMR exome

AF:

0.000241

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00678

Gnomad4 NFE exome

AF:

0.00102

Gnomad4 OTH exome

AF:

0.000920

GnomAD4 genome

AF:

0.00116

AC:

128

AN:

110435

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

33093

show subpopulations

Gnomad4 AFR

AF:

0.000195

Gnomad4 AMR

AF:

0.000194

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00742

Gnomad4 NFE

AF:

0.00150

Gnomad4 OTH

AF:

0.000665

Alfa

AF:

0.00121

Hom.:

Bravo

AF:

0.000676

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00179

AC:

ExAC

AF:

0.00131

AC:

159

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Benign:2

Jan 18, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Oct 15, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

MAGT1-related disorder

Benign:1

Mar 06, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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;C5231393:Congenital disorder of glycosylation, type ICC

Benign:1

May 19, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Pathogenic

0.46

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.30

T;T;T

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.65

.;T;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-0.45

MutationAssessor

Uncertain

2.2

.;.;M

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.4

N;.;.

REVEL

Uncertain

0.62

Sift

Pathogenic

0.0

D;.;.

Sift4G

Uncertain

0.010

D;D;D

Polyphen

0.0030

.;.;B

Vest4

0.48

MVP

0.99

MPC

0.62

ClinPred

0.093

GERP RS

5.5

Varity_R

0.49

gMVP

0.94

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