Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000618282.5(MAGT1):c.651T>A(p.Thr217Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00285 in 1,207,966 control chromosomes in the GnomAD database, including 51 homozygotes. There are 889 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 27 hom., 430 hem., cov: 23)

Exomes 𝑓: 0.0016 ( 24 hom. 459 hem. )

Consequence

MAGT1
ENST00000618282.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.35

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: Unknown, XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant X-77856754-A-T is Benign according to our data. Variant chrX-77856754-A-T is described in ClinVar as Benign. ClinVar VariationId is 129568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.35 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.015 (1678/111891) while in subpopulation AFR AF = 0.0514 (1587/30856). AF 95% confidence interval is 0.0493. There are 27 homozygotes in GnomAd4. There are 430 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 27 XL,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000618282.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGT1	NM_001367916.1	MANE Select	c.651T>A	p.Thr217Thr	synonymous	Exon 5 of 10	NP_001354845.1
	MAGT1	NM_032121.5		c.747T>A	p.Thr249Thr	synonymous	Exon 5 of 10	NP_115497.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MAGT1	ENST00000618282.5	TSL:1 MANE Select	c.651T>A	p.Thr217Thr	synonymous	Exon 5 of 10	ENSP00000480732.1
MAGT1	ENST00000358075.11	TSL:1	c.651T>A	p.Thr217Thr	synonymous	Exon 5 of 10	ENSP00000354649.6
MAGT1	ENST00000685015.1		c.651T>A	p.Thr217Thr	synonymous	Exon 5 of 9	ENSP00000509969.1

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

1676

AN:

111837

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0515

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00452

Gnomad ASJ

AF:

0.00415

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000370

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000169

Gnomad OTH

AF:

0.0161

GnomAD2 exomes

AF:

0.00449

AC:

820

AN:

182455

AF XY:

0.00268

show subpopulations

Gnomad AFR exome

AF:

0.0534

Gnomad AMR exome

AF:

0.00289

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000857

Gnomad OTH exome

AF:

0.00200

GnomAD4 exome

AF:

0.00161

AC:

1770

AN:

1096075

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

459

AN XY:

361585

show subpopulations

African (AFR)

AF:

0.0513

AC:

1352

AN:

26365

American (AMR)

AF:

0.00330

AC:

116

AN:

35154

Ashkenazi Jewish (ASJ)

AF:

0.00331

AC:

AN:

19363

East Asian (EAS)

AF:

0.00

AC:

AN:

30139

South Asian (SAS)

AF:

0.000278

AC:

AN:

53863

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40516

Middle Eastern (MID)

AF:

0.000969

AC:

AN:

4128

European-Non Finnish (NFE)

AF:

0.0000523

AC:

AN:

840538

Other (OTH)

AF:

0.00380

AC:

175

AN:

46009

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

137

206

274

343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.0150

AC:

1678

AN:

111891

Hom.:

Cov.:

AF XY:

0.0126

AC XY:

430

AN XY:

34091

show subpopulations

African (AFR)

AF:

0.0514

AC:

1587

AN:

30856

American (AMR)

AF:

0.00451

AC:

AN:

10412

Ashkenazi Jewish (ASJ)

AF:

0.00415

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3571

South Asian (SAS)

AF:

0.00

AC:

AN:

2693

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6028

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.000169

AC:

AN:

53268

Other (OTH)

AF:

0.0159

AC:

AN:

1514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

127

190

254

317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00844

Hom.:

Bravo

AF:

0.0171

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (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

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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.

rs61732679

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over