X-77830970-TTTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTA-TTTTTA

Variant names:

• chrX-77830970-TTTTTATTTTATTTTATTTTATTTTATTTTATTTTA-T
• rs201564456
• NM_001367916.1:c.902-110_902-76delTAAAATAAAATAAAATAAAATAAAATAAAATAAAA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001367916.1(MAGT1):​c.902-110_902-76delTAAAATAAAATAAAATAAAATAAAATAAAATAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00437 in 182,564 control chromosomes in the GnomAD database, including 20 homozygotes. There are 307 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0023 (0 hom., 51 hem., cov: 0)
  • Exomes 𝑓: 0.0062 (20 hom. 256 hem.)
• Consequence: MAGT1 NM_001367916.1 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAd4 at 51 XL,Unknown gene

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.902-110_902-76delTAAAATAAAATAAAATAAAATAAAATAAAATAAAA		intron	N/A	NP_001354845.1	Q9H0U3-1
	MAGT1	NM_032121.5		c.998-110_998-76delTAAAATAAAATAAAATAAAATAAAATAAAATAAAA		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.902-110_902-76delTAAAATAAAATAAAATAAAATAAAATAAAATAAAA		intron	N/A	ENSP00000480732.1	Q9H0U3-1
	MAGT1	ENST00000358075.11	TSL:1	c.902-110_902-76delTAAAATAAAATAAAATAAAATAAAATAAAATAAAA		intron	N/A	ENSP00000354649.6	Q9H0U3-1
	MAGT1	ENST00000685015.1		c.902-4196_902-4162delTAAAATAAAATAAAATAAAATAAAATAAAATAAAA		intron	N/A	ENSP00000509969.1	A0A8I5QKX7

Frequencies

GnomAD3 genomes AF: 0.00233 AC: 203 AN: 87205 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000343

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000399

Gnomad ASJ AF: 0.00128

Gnomad EAS AF: 0.000342

Gnomad SAS AF: 0.000548

Gnomad FIN AF: 0.0146

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00339

Gnomad OTH AF: 0.000901

GnomAD4 exome AF: 0.00623 AC: 594 AN: 95362 Hom.: 20 AF XY: 0.0104 AC XY: 256 AN XY: 24522

African (AFR) AF: 0.00 AC: 0 AN: 1984

American (AMR) AF: 0.00 AC: 0 AN: 3719

Ashkenazi Jewish (ASJ) AF: 0.00167 AC: 5 AN: 2998

East Asian (EAS) AF: 0.00 AC: 0 AN: 5359

South Asian (SAS) AF: 0.000189 AC: 1 AN: 5294

European-Finnish (FIN) AF: 0.0149 AC: 223 AN: 14963

Middle Eastern (MID) AF: 0.00331 AC: 2 AN: 605

European-Non Finnish (NFE) AF: 0.00611 AC: 345 AN: 56425

Other (OTH) AF: 0.00448 AC: 18 AN: 4015

GnomAD4 genome AF: 0.00233 AC: 203 AN: 87202 Hom.: 0 Cov.: 0 AF XY: 0.00316 AC XY: 51 AN XY: 16146

African (AFR) AF: 0.000343 AC: 8 AN: 23321

American (AMR) AF: 0.000398 AC: 3 AN: 7535

Ashkenazi Jewish (ASJ) AF: 0.00128 AC: 3 AN: 2346

East Asian (EAS) AF: 0.000343 AC: 1 AN: 2914

South Asian (SAS) AF: 0.000553 AC: 1 AN: 1809

European-Finnish (FIN) AF: 0.0146 AC: 33 AN: 2261

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 172

European-Non Finnish (NFE) AF: 0.00339 AC: 153 AN: 45140

Other (OTH) AF: 0.000887 AC: 1 AN: 1128

Alfa AF: 0.0134 Hom.: 943

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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

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;