rs182757967

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_032121.5(MAGT1):c.67G>A(p.Val23Ile) variant causes a missense 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. 13/19 in silico tools predict 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
NM_032121.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.04

Publications

1 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=0.016403139).

BP6

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

BS2

High Hemizygotes in GnomAd4 at 14 XL,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032121.5. 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_032121.5		c.67G>A	p.Val23Ile	missense	Exon 1 of 10	NP_115497.4	Q9H0U3
	MAGT1	NM_001367916.1	MANE Select	c.-30G>A		upstream_gene	N/A	NP_001354845.1	Q9H0U3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MAGT1	ENST00000358075.11	TSL:1	c.-30G>A	5_prime_UTR	Exon 1 of 10	ENSP00000354649.6	Q9H0U3-1
MAGT1	ENST00000373336.3	TSL:1	c.-30G>A	5_prime_UTR	Exon 1 of 4	ENSP00000362433.3	Q9H0U3-2
MAGT1	ENST00000944450.1		c.-30G>A	5_prime_UTR	Exon 1 of 9	ENSP00000614509.1

Frequencies

GnomAD3 genomes

AF:

0.000488

AC:

AN:

112731

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000677

AC:

114

AN:

168288

AF XY:

0.000599

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 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

African (AFR)

AF:

0.0000761

AC:

AN:

26274

American (AMR)

AF:

0.00

AC:

AN:

34473

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19256

East Asian (EAS)

AF:

0.00

AC:

AN:

29937

South Asian (SAS)

AF:

0.0000188

AC:

AN:

53184

European-Finnish (FIN)

AF:

0.00219

AC:

AN:

40132

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4126

European-Non Finnish (NFE)

AF:

0.000706

AC:

592

AN:

838183

Other (OTH)

AF:

0.00122

AC:

AN:

45833

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

122

153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000488

AC:

AN:

112784

Hom.:

Cov.:

AF XY:

0.000401

AC XY:

AN XY:

34934

show subpopulations

African (AFR)

AF:

0.000161

AC:

AN:

31139

American (AMR)

AF:

0.00

AC:

AN:

10696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2659

East Asian (EAS)

AF:

0.00

AC:

AN:

3585

South Asian (SAS)

AF:

0.00

AC:

AN:

2762

European-Finnish (FIN)

AF:

0.00162

AC:

AN:

6189

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.000750

AC:

AN:

53317

Other (OTH)

AF:

0.00

AC:

AN:

1537

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.000668

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

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

MAGT1-related disorder (1)

X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.086

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.49

M_CAP

Benign

0.0092

MetaRNN

Benign

0.016

MetaSVM

Benign

-1.0

PhyloP100

2.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.070

REVEL

Benign

0.079

Sift

Benign

0.24

Sift4G

Benign

0.16

Vest4

0.28

MVP

0.43

MPC

0.39

ClinPred

0.032

GERP RS

4.6

PromoterAI

-0.27

Neutral

(source)

gMVP

0.15

Mutation Taster

=283/17

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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