NM_001367916.1:c.932T>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia
Inheritance: XL, Unknown Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
intellectual disability, X-linked 95
Inheritance: XL Classification: LIMITED Submitted by: G2P
X-linked intellectual disability
Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

MAGT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 96213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 44 XL,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367916.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGT1	NM_001367916.1	MANE Select	c.932T>G	p.Val311Gly	missense	Exon 9 of 10	NP_001354845.1	Q9H0U3-1
	MAGT1	NM_032121.5		c.1028T>G	p.Val343Gly	missense	Exon 9 of 10	NP_115497.4	Q9H0U3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAGT1	ENST00000618282.5	TSL:1 MANE Select	c.932T>G	p.Val311Gly	missense	Exon 9 of 10	ENSP00000480732.1	Q9H0U3-1
MAGT1	ENST00000358075.11	TSL:1	c.932T>G	p.Val311Gly	missense	Exon 9 of 10	ENSP00000354649.6	Q9H0U3-1
MAGT1	ENST00000688650.1		c.842T>G	p.Val281Gly	missense	Exon 8 of 9	ENSP00000509785.1	A0A8I5KYH1

Frequencies

GnomAD3 genomes

AF:

0.00116

AC:

128

AN:

110401

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00153

AC:

260

AN:

169941

AF XY:

0.00154

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 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

African (AFR)

AF:

0.000160

AC:

AN:

25005

American (AMR)

AF:

0.000241

AC:

AN:

33170

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18186

East Asian (EAS)

AF:

0.00

AC:

AN:

28322

South Asian (SAS)

AF:

0.00

AC:

AN:

47717

European-Finnish (FIN)

AF:

0.00678

AC:

262

AN:

38667

Middle Eastern (MID)

AF:

0.000255

AC:

AN:

3918

European-Non Finnish (NFE)

AF:

0.00102

AC:

821

AN:

808591

Other (OTH)

AF:

0.000920

AC:

AN:

43493

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

102

136

170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00116

AC:

128

AN:

110435

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

33093

show subpopulations

African (AFR)

AF:

0.000195

AC:

AN:

30693

American (AMR)

AF:

0.000194

AC:

AN:

10322

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2632

East Asian (EAS)

AF:

0.00

AC:

AN:

3548

South Asian (SAS)

AF:

0.00

AC:

AN:

2715

European-Finnish (FIN)

AF:

0.00742

AC:

AN:

5389

Middle Eastern (MID)

AF:

0.00

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.00150

AC:

AN:

52734

Other (OTH)

AF:

0.000665

AC:

AN:

1503

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00114

Hom.:

Bravo

AF:

0.000676

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00179

AC:

ExAC

AF:

0.00131

AC:

159

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia (2)

MAGT1-related disorder (1)

not specified (1)

X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia;C5231393:Congenital disorder of glycosylation, type ICC (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Pathogenic

0.46

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.30

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.65

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.45

MutationAssessor

Uncertain

2.2

PhyloP100

8.1

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.62

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.010

Polyphen

0.0030

Vest4

0.48

MVP

0.99

MPC

0.62

ClinPred

0.093

GERP RS

5.5

Varity_R

0.49

gMVP

0.94

Mutation Taster

=60/40

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over