X-77830970-TTTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTA-TTTTTATTTTATTTTATTTTATTTTA

Variant names:

• chrX-77830970-TTTTTATTTTATTTTA-T
• rs201564456
• NM_001367916.1:c.902-90_902-76delTAAAATAAAATAAAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001367916.1(MAGT1):​c.902-90_902-76delTAAAATAAAATAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0193 in 95,309 control chromosomes in the GnomAD database, including 38 homozygotes. There are 555 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 0.073 (259 hom., 978 hem., cov: 0)
  • Exomes 𝑓: 0.019 (38 hom. 555 hem.)
  • Failed GnomAD Quality Control
• 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-TTTTTATTTTATTTTA-T is Benign according to our data. Variant chrX-77830970-TTTTTATTTTATTTTA-T is described in ClinVar as Benign. ClinVar VariationId is 1228783.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.0193 (1841/95309) while in subpopulation AFR AF = 0.0314 (62/1977). AF 95% confidence interval is 0.0251. There are 38 homozygotes in GnomAdExome4. There are 555 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 38 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.902-90_902-76delTAAAATAAAATAAAA		intron	N/A	NP_001354845.1	Q9H0U3-1
	MAGT1	NM_032121.5		c.998-90_998-76delTAAAATAAAATAAAA		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.902-90_902-76delTAAAATAAAATAAAA		intron	N/A	ENSP00000480732.1	Q9H0U3-1
	MAGT1	ENST00000358075.11	TSL:1	c.902-90_902-76delTAAAATAAAATAAAA		intron	N/A	ENSP00000354649.6	Q9H0U3-1
	MAGT1	ENST00000685015.1		c.902-4176_902-4162delTAAAATAAAATAAAA		intron	N/A	ENSP00000509969.1	A0A8I5QKX7

Frequencies

GnomAD3 genomes AF: 0.0727 AC: 6338 AN: 87126 Hom.: 260 Cov.: 0

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.0464

Gnomad ASJ AF: 0.0375

Gnomad EAS AF: 0.0540

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0208

Gnomad MID AF: 0.126

Gnomad NFE AF: 0.0652

Gnomad OTH AF: 0.0749

GnomAD4 exome AF: 0.0193 AC: 1841 AN: 95309 Hom.: 38 AF XY: 0.0227 AC XY: 555 AN XY: 24483

African (AFR) AF: 0.0314 AC: 62 AN: 1977

American (AMR) AF: 0.0108 AC: 40 AN: 3716

Ashkenazi Jewish (ASJ) AF: 0.00836 AC: 25 AN: 2992

East Asian (EAS) AF: 0.0101 AC: 54 AN: 5358

South Asian (SAS) AF: 0.00151 AC: 8 AN: 5293

European-Finnish (FIN) AF: 0.0188 AC: 281 AN: 14958

Middle Eastern (MID) AF: 0.00496 AC: 3 AN: 605

European-Non Finnish (NFE) AF: 0.0226 AC: 1277 AN: 56398

Other (OTH) AF: 0.0227 AC: 91 AN: 4012

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0728 AC: 6343 AN: 87123 Hom.: 259 Cov.: 0 AF XY: 0.0607 AC XY: 978 AN XY: 16107

African (AFR) AF: 0.107 AC: 2492 AN: 23288

American (AMR) AF: 0.0464 AC: 349 AN: 7528

Ashkenazi Jewish (ASJ) AF: 0.0375 AC: 88 AN: 2344

East Asian (EAS) AF: 0.0536 AC: 156 AN: 2911

South Asian (SAS) AF: 0.0227 AC: 41 AN: 1809

European-Finnish (FIN) AF: 0.0208 AC: 47 AN: 2257

Middle Eastern (MID) AF: 0.134 AC: 23 AN: 172

European-Non Finnish (NFE) AF: 0.0652 AC: 2940 AN: 45117

Other (OTH) AF: 0.0764 AC: 86 AN: 1126

Alfa AF: 0.0425 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: COSV63782188;