rs387906724

Variant names:

• chrX-77870885-G-A
• rs387906724
• NM_001367916.1:c.313C>T

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The ENST00000618282.5(MAGT1):​c.313C>T​(p.Arg105*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 23)
• Consequence: MAGT1 ENST00000618282.5 stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 2.34
• Publications: 6 publications found

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

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-77870885-G-A is Pathogenic according to our data. Variant chrX-77870885-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 29982.Status of the report is criteria_provided_single_submitter, 1 stars.

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.313C>T	p.Arg105*	stop_gained	Exon 3 of 10	NP_001354845.1
	MAGT1	NM_032121.5		c.409C>T	p.Arg137*	stop_gained	Exon 3 of 10	NP_115497.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGT1	ENST00000618282.5	TSL:1 MANE Select	c.313C>T	p.Arg105*	stop_gained	Exon 3 of 10	ENSP00000480732.1
	MAGT1	ENST00000358075.11	TSL:1	c.313C>T	p.Arg105*	stop_gained	Exon 3 of 10	ENSP00000354649.6
	MAGT1	ENST00000373336.3	TSL:1	c.313C>T	p.Arg105*	stop_gained	Exon 3 of 4	ENSP00000362433.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	not provided (1)
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_addAF	Pathogenic	0.66	D
BayesDel_noAF	Pathogenic	0.47
CADD	Pathogenic	34
DANN	Uncertain	1.0
FATHMM_MKL	Benign	0.76	D
PhyloP100		2.3
Vest4		0.88
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=4/196	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs387906724; hg19: chrX-77126382; COSMIC: COSV63781525;