rs370329684

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000358075.11(MAGT1):c.-39C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000175 in 1,199,285 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 4 hem., cov: 24)

Exomes 𝑓: 0.0000083 ( 0 hom. 4 hem. )

Consequence

MAGT1
ENST00000358075.11 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.466

Publications

0 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

new If you want to explore the variant's impact on the transcript ENST00000358075.11, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04292354).

BP6

Variant X-77895449-G-A is Benign according to our data. Variant chrX-77895449-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 539315.

BS2

High Hemizygotes in GnomAd4 at 4 XL,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000358075.11. 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.58C>T	p.Arg20Trp	missense	Exon 1 of 10	NP_115497.4	Q9H0U3
	MAGT1	NM_001367916.1	MANE Select	c.-39C>T		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.-39C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	ENSP00000354649.6	Q9H0U3-1
MAGT1	ENST00000358075.11	TSL:1	c.-39C>T	5_prime_UTR	Exon 1 of 10	ENSP00000354649.6	Q9H0U3-1
MAGT1	ENST00000944450.1		c.-39C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000614509.1

Frequencies

GnomAD3 genomes

AF:

0.000107

AC:

AN:

112495

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000387

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000377

AC:

AN:

159213

AF XY:

0.0000401

show subpopulations

Gnomad AFR exome

AF:

0.000435

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000148

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000828

AC:

AN:

1086790

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

354612

show subpopulations

African (AFR)

AF:

0.000191

AC:

AN:

26180

American (AMR)

AF:

0.00

AC:

AN:

33803

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19165

East Asian (EAS)

AF:

0.00

AC:

AN:

29697

South Asian (SAS)

AF:

0.0000190

AC:

AN:

52746

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39891

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4121

European-Non Finnish (NFE)

AF:

0.00000359

AC:

AN:

835557

Other (OTH)

AF:

0.00

AC:

AN:

45630

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000107

AC:

AN:

112495

Hom.:

Cov.:

AF XY:

0.000115

AC XY:

AN XY:

34689

show subpopulations

African (AFR)

AF:

0.000387

AC:

AN:

30984

American (AMR)

AF:

0.00

AC:

AN:

10645

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3599

South Asian (SAS)

AF:

0.00

AC:

AN:

2760

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6139

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53279

Other (OTH)

AF:

0.00

AC:

AN:

1520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000786

Hom.:

Bravo

AF:

0.000102

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (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

0.14

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.9

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.095

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.50

M_CAP

Benign

0.0080

MetaRNN

Benign

0.043

MetaSVM

Benign

-1.0

PhyloP100

0.47

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.43

REVEL

Benign

0.049

Sift

Benign

0.058

Sift4G

Uncertain

0.010

PromoterAI

-0.16

Neutral

(source)

gMVP

0.24

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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