rs140854076

Positions:

• chrX-77895395-G-A
• chrX-77895395-G-C
• chrX-77895395-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001367916.1(MAGT1):​c.16C>T​(p.Arg6Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,210,302 control chromosomes in the GnomAD database, including 5 homozygotes. There are 1,160 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 Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., 66 hem., cov: 24)
  • Exomes 𝑓: 0.0027 (5 hom. 1094 hem.)
• Consequence: MAGT1 NM_001367916.1 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: 0.650

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003437698).
• BP6: Variant X-77895395-G-A is Benign according to our data. Variant chrX-77895395-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 96214.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1, Benign=2}. Variant chrX-77895395-G-A is described in Lovd as [Likely_benign].
• BS2: High Hemizygotes in GnomAd4 at 66 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGT1	NM_001367916.1	c.16C>T	p.Arg6Trp	missense_variant	1/10	ENST00000618282.5	NP_001354845.1
MAGT1	NM_032121.5	c.112C>T	p.Arg38Trp	missense_variant	1/10		NP_115497.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGT1	ENST00000618282.5	c.16C>T	p.Arg6Trp	missense_variant	1/10	1	NM_001367916.1	ENSP00000480732.1

Frequencies

GnomAD3 genomes AF: 0.00178 AC: 200 AN: 112325 Hom.: 0 Cov.: 24 AF XY: 0.00194 AC XY: 67 AN XY: 34489

Gnomad AFR AF: 0.000291

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000942

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0102

Gnomad FIN AF: 0.000820

Gnomad MID AF: 0.00417

Gnomad NFE AF: 0.00287

Gnomad OTH AF: 0.00198

GnomAD3 exomes AF: 0.00233 AC: 425 AN: 182634 Hom.: 1 AF XY: 0.00301 AC XY: 202 AN XY: 67180

Gnomad AFR exome AF: 0.0000763

Gnomad AMR exome AF: 0.000292

Gnomad ASJ exome AF: 0.000134

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00898

Gnomad FIN exome AF: 0.000939

Gnomad NFE exome AF: 0.00279

Gnomad OTH exome AF: 0.000665

GnomAD4 exome AF: 0.00266 AC: 2924 AN: 1097926 Hom.: 5 Cov.: 31 AF XY: 0.00301 AC XY: 1094 AN XY: 363286

Gnomad4 AFR exome AF: 0.000227

Gnomad4 AMR exome AF: 0.000313

Gnomad4 ASJ exome AF: 0.000155

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00843

Gnomad4 FIN exome AF: 0.000864

Gnomad4 NFE exome AF: 0.00276

Gnomad4 OTH exome AF: 0.00180

GnomAD4 genome AF: 0.00177 AC: 199 AN: 112376 Hom.: 0 Cov.: 24 AF XY: 0.00191 AC XY: 66 AN XY: 34550

Gnomad4 AFR AF: 0.000290

Gnomad4 AMR AF: 0.0000940

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00987

Gnomad4 FIN AF: 0.000820

Gnomad4 NFE AF: 0.00287

Gnomad4 OTH AF: 0.00196

Alfa AF: 0.00247 Hom.: 107

Bravo AF: 0.00136

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00277 AC: 8

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00283 AC: 19

ExAC AF: 0.00287 AC: 349

EpiCase AF: 0.00284

EpiControl AF: 0.00273

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:3

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1 Benign:1

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 09, 2021	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 13, 2013	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 26, 2021

- -

X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.94
DEOGEN2	Benign	0.095	T;T;T;.
FATHMM_MKL	Benign	0.0048	N
LIST_S2	Benign	0.31	.;T;T;T
MetaRNN	Benign	0.0034	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	.;.;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.39	N;.;.;N
REVEL	Benign	0.033
Sift	Benign	0.32	T;.;.;T
Sift4G	Benign	0.066	T;T;T;T
Polyphen		0.0	.;.;B;.
Vest4		0.074
MVP		0.093
MPC		0.49
ClinPred		0.014	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.10
gMVP		0.23

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

Other links and lift over

dbSNP: rs140854076; hg19: chrX-77150892;