X-77830970-TTTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTA-TTTTTATTTTATTTTATTTTA

Variant names:

• chrX-77830970-TTTTTATTTTATTTTATTTTA-T
• rs201564456
• NM_001367916.1:c.902-95_902-76delTAAAATAAAATAAAATAAAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001367916.1(MAGT1):​c.902-95_902-76delTAAAATAAAATAAAATAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 181,886 control chromosomes in the GnomAD database, including 16,420 homozygotes. There are 17,634 hemizygotes in GnomAD. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (10163 hom., 7642 hem., cov: 0)
  • Exomes 𝑓: 0.30 (6257 hom. 9992 hem.)
• Consequence: MAGT1 NM_001367916.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.455
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant X-77830970-TTTTTATTTTATTTTATTTTA-T is Benign according to our data. Variant chrX-77830970-TTTTTATTTTATTTTATTTTA-T is described in ClinVar as Benign. ClinVar VariationId is 1294401.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

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.902-95_902-76delTAAAATAAAATAAAATAAAA		intron	N/A	NP_001354845.1	Q9H0U3-1
	MAGT1	NM_032121.5		c.998-95_998-76delTAAAATAAAATAAAATAAAA		intron	N/A	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.902-95_902-76delTAAAATAAAATAAAATAAAA		intron	N/A	ENSP00000480732.1	Q9H0U3-1
	MAGT1	ENST00000358075.11	TSL:1	c.902-95_902-76delTAAAATAAAATAAAATAAAA		intron	N/A	ENSP00000354649.6	Q9H0U3-1
	MAGT1	ENST00000685015.1		c.902-4181_902-4162delTAAAATAAAATAAAATAAAA		intron	N/A	ENSP00000509969.1	A0A8I5QKX7

Frequencies

GnomAD3 genomes AF: 0.485 AC: 42131 AN: 86911 Hom.: 10175 Cov.: 0

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.445

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.521

GnomAD4 exome AF: 0.304 AC: 28916 AN: 94978 Hom.: 6257 AF XY: 0.413 AC XY: 9992 AN XY: 24192

African (AFR) AF: 0.0571 AC: 113 AN: 1979

American (AMR) AF: 0.218 AC: 810 AN: 3712

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 652 AN: 2986

East Asian (EAS) AF: 0.222 AC: 1187 AN: 5347

South Asian (SAS) AF: 0.0668 AC: 353 AN: 5285

European-Finnish (FIN) AF: 0.517 AC: 7712 AN: 14913

Middle Eastern (MID) AF: 0.119 AC: 72 AN: 604

European-Non Finnish (NFE) AF: 0.299 AC: 16794 AN: 56156

Other (OTH) AF: 0.306 AC: 1223 AN: 3996

GnomAD4 genome AF: 0.484 AC: 42105 AN: 86908 Hom.: 10163 Cov.: 0 AF XY: 0.481 AC XY: 7642 AN XY: 15896

African (AFR) AF: 0.134 AC: 3125 AN: 23292

American (AMR) AF: 0.599 AC: 4494 AN: 7506

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 1575 AN: 2335

East Asian (EAS) AF: 0.430 AC: 1248 AN: 2901

South Asian (SAS) AF: 0.447 AC: 806 AN: 1802

European-Finnish (FIN) AF: 0.676 AC: 1517 AN: 2243

Middle Eastern (MID) AF: 0.424 AC: 73 AN: 172

European-Non Finnish (NFE) AF: 0.631 AC: 28357 AN: 44972

Other (OTH) AF: 0.515 AC: 576 AN: 1118

Alfa AF: 0.441 Hom.: 943

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs201564456; hg19: chrX-77086467; COSMIC: COSV63781557;