X-77830864-TACA-T

Variant names:

• chrX-77830864-TACA-T
• rs2076895612
• NM_001367916.1:c.930_932delTGT

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_001367916.1(MAGT1):​c.930_932delTGT​(p.Val311del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000191 in 1,046,619 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000019 (0 hom. 1 hem.)
• Consequence: MAGT1 NM_001367916.1 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.11
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001367916.1. Strenght limited to Supporting due to length of the change: 1aa.

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.930_932delTGT	p.Val311del	disruptive_inframe_deletion	Exon 9 of 10	NP_001354845.1	Q9H0U3-1
	MAGT1	NM_032121.5		c.1026_1028delTGT	p.Val343del	disruptive_inframe_deletion	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.930_932delTGT	p.Val311del	disruptive_inframe_deletion	Exon 9 of 10	ENSP00000480732.1	Q9H0U3-1
	MAGT1	ENST00000358075.11	TSL:1	c.930_932delTGT	p.Val311del	disruptive_inframe_deletion	Exon 9 of 10	ENSP00000354649.6	Q9H0U3-1
	MAGT1	ENST00000688650.1		c.840_842delTGT	p.Val281del	disruptive_inframe_deletion	Exon 8 of 9	ENSP00000509785.1	A0A8I5KYH1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000191 AC: 2 AN: 1046619 Hom.: 0 AF XY: 0.00000304 AC XY: 1 AN XY: 328589

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25001

American (AMR) AF: 0.00 AC: 0 AN: 33150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18163

East Asian (EAS) AF: 0.00 AC: 0 AN: 28267

South Asian (SAS) AF: 0.00 AC: 0 AN: 47728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3915

European-Non Finnish (NFE) AF: 0.00000247 AC: 2 AN: 808315

Other (OTH) AF: 0.00 AC: 0 AN: 43458

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

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
PhyloP100		8.1

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

Other links and lift over

dbSNP: rs2076895612; hg19: chrX-77086361;