Genetic Variant MAGT1:p.Arg6Gly (chrX-77895395-G-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001367916.1(MAGT1):c.16C>G(p.Arg6Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,210,259 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000028 ( 0 hom. 12 hem. )

Consequence

MAGT1
NM_001367916.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.650

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14131644).

BS2

High Hemizygotes in GnomAdExome4 at 12 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGT1	NM_001367916.1 link	c.16C>G	p.Arg6Gly	missense_variant	Exon 1 of 10	ENST00000618282.5	NP_001354845.1
MAGT1	NM_032121.5 link	c.112C>G	p.Arg38Gly	missense_variant	Exon 1 of 10		NP_115497.4	Q9H0U3A0A087WU53

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGT1	ENST00000618282.5 link	c.16C>G	p.Arg6Gly	missense_variant	Exon 1 of 10	1	NM_001367916.1	ENSP00000480732.1		Q9H0U3-1

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112327

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34489

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000110

AC:

AN:

182634

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

67180

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000246

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000282

AC:

AN:

1097932

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

363288

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000356

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112327

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34489

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.11

T;T;T;.

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.37

.;T;T;T

M_CAP

Benign

0.0076

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

.;.;L;L

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.77

N;.;.;N

REVEL

Benign

0.031

Sift

Benign

0.26

T;.;.;T

Sift4G

Benign

0.22

T;T;T;T

Polyphen

0.011

.;.;B;.

Vest4

0.27

MutPred

0.60

.;.;Loss of methylation at R6 (P = 0.0257);Loss of methylation at R6 (P = 0.0257);

MVP

0.20

MPC

0.62

ClinPred

0.040

GERP RS

2.0

Varity_R

0.15

gMVP

0.17

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over