X-77830970-TTTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTA-TTTTTATTTTATTTTATTTTATTTTATTTTATTTTA

Variant names:

• chrX-77830970-TTTTTA-T
• rs201564456
• NM_001367916.1:c.902-80_902-76delTAAAA

Variant summary

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

The NM_001367916.1(MAGT1):​c.902-80_902-76delTAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 181,983 control chromosomes in the GnomAD database, including 2,576 homozygotes. There are 3,732 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (2197 hom., 2475 hem., cov: 0)
  • Exomes 𝑓: 0.058 (379 hom. 1257 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-TTTTTA-T is Benign according to our data. Variant chrX-77830970-TTTTTA-T is described in ClinVar as Benign. ClinVar VariationId is 1296390.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.309 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.902-80_902-76delTAAAA		intron	N/A	NP_001354845.1	Q9H0U3-1
	MAGT1	NM_032121.5		c.998-80_998-76delTAAAA		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.902-80_902-76delTAAAA		intron	N/A	ENSP00000480732.1	Q9H0U3-1
	MAGT1	ENST00000358075.11	TSL:1	c.902-80_902-76delTAAAA		intron	N/A	ENSP00000354649.6	Q9H0U3-1
	MAGT1	ENST00000685015.1		c.902-4166_902-4162delTAAAA		intron	N/A	ENSP00000509969.1	A0A8I5QKX7

Frequencies

GnomAD3 genomes AF: 0.218 AC: 18949 AN: 86927 Hom.: 2196 Cov.: 0

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.0521

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.00956

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.204

GnomAD4 exome AF: 0.0580 AC: 5516 AN: 95059 Hom.: 379 AF XY: 0.0515 AC XY: 1257 AN XY: 24405

African (AFR) AF: 0.0531 AC: 105 AN: 1977

American (AMR) AF: 0.0277 AC: 103 AN: 3712

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 57 AN: 2995

East Asian (EAS) AF: 0.00336 AC: 18 AN: 5359

South Asian (SAS) AF: 0.00567 AC: 30 AN: 5290

European-Finnish (FIN) AF: 0.156 AC: 2328 AN: 14885

Middle Eastern (MID) AF: 0.0182 AC: 11 AN: 605

European-Non Finnish (NFE) AF: 0.0476 AC: 2675 AN: 56235

Other (OTH) AF: 0.0472 AC: 189 AN: 4001

GnomAD4 genome AF: 0.218 AC: 18959 AN: 86924 Hom.: 2197 Cov.: 0 AF XY: 0.154 AC XY: 2475 AN XY: 16104

African (AFR) AF: 0.315 AC: 7329 AN: 23235

American (AMR) AF: 0.161 AC: 1210 AN: 7499

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 294 AN: 2342

East Asian (EAS) AF: 0.00961 AC: 28 AN: 2914

South Asian (SAS) AF: 0.117 AC: 211 AN: 1805

European-Finnish (FIN) AF: 0.170 AC: 383 AN: 2248

Middle Eastern (MID) AF: 0.186 AC: 32 AN: 172

European-Non Finnish (NFE) AF: 0.205 AC: 9216 AN: 45005

Other (OTH) AF: 0.200 AC: 226 AN: 1128

Alfa AF: 0.189 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;