NM_001367916.1:c.948G>A

Variant names:

• chrX-77830849-C-T
• rs2076895533
• NM_001367916.1:c.948G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Moderate PM2 PP5_Moderate

The NM_001367916.1(MAGT1):​c.948G>A​(p.Trp316*) variant causes a stop gained change. 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 (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAGT1 NM_001367916.1 stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.04
• Publications: 0 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: 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

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0595 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-77830849-C-T is Pathogenic according to our data. Variant chrX-77830849-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 976322.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367916.1. 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_001367916.1	MANE Select	c.948G>A	p.Trp316*	stop_gained	Exon 9 of 10	NP_001354845.1	Q9H0U3-1
	MAGT1	NM_032121.5		c.1044G>A	p.Trp348*	stop_gained	Exon 9 of 10	NP_115497.4	Q9H0U3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGT1	ENST00000618282.5	TSL:1 MANE Select	c.948G>A	p.Trp316*	stop_gained	Exon 9 of 10	ENSP00000480732.1	Q9H0U3-1
	MAGT1	ENST00000358075.11	TSL:1	c.948G>A	p.Trp316*	stop_gained	Exon 9 of 10	ENSP00000354649.6	Q9H0U3-1
	MAGT1	ENST00000688650.1		c.858G>A	p.Trp286*	stop_gained	Exon 8 of 9	ENSP00000509785.1	A0A8I5KYH1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1050226 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 331624

African (AFR) AF: 0.00 AC: 0 AN: 25060

American (AMR) AF: 0.00 AC: 0 AN: 33196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18207

East Asian (EAS) AF: 0.00 AC: 0 AN: 28339

South Asian (SAS) AF: 0.00 AC: 0 AN: 47898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38662

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3932

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 811308

Other (OTH) AF: 0.00 AC: 0 AN: 43624

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
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	0.62
CADD	Pathogenic	37
DANN	Uncertain	1.0
FATHMM_MKL	Uncertain	0.89	D
PhyloP100		4.0
Vest4		0.67
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=6/194	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs2076895533; hg19: chrX-77086346;