X-77830970-TTTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTA-TTTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTA

Variant names:

• chrX-77830970-T-TTTTTATTTTA
• rs201564456
• NM_001367916.1:c.902-85_902-76dupTAAAATAAAA

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001367916.1(MAGT1):​c.902-85_902-76dupTAAAATAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 95,360 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 31 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0094 (11 hom., 106 hem., cov: 0)
  • Exomes 𝑓: 0.0013 (0 hom. 31 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAGT1 NM_001367916.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.701
• 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 -6 ACMG points.

• BP6: Variant X-77830970-T-TTTTTATTTTA is Benign according to our data. Variant chrX-77830970-T-TTTTTATTTTA is described in ClinVar as Likely_benign. ClinVar VariationId is 1211779.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 31 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.902-85_902-76dupTAAAATAAAA		intron	N/A	NP_001354845.1	Q9H0U3-1
	MAGT1	NM_032121.5		c.998-85_998-76dupTAAAATAAAA		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.902-76_902-75insTAAAATAAAA		intron	N/A	ENSP00000480732.1	Q9H0U3-1
	MAGT1	ENST00000358075.11	TSL:1	c.902-76_902-75insTAAAATAAAA		intron	N/A	ENSP00000354649.6	Q9H0U3-1
	MAGT1	ENST00000685015.1		c.902-4162_902-4161insTAAAATAAAA		intron	N/A	ENSP00000509969.1	A0A8I5QKX7

Frequencies

GnomAD3 genomes AF: 0.00939 AC: 819 AN: 87185 Hom.: 11 Cov.: 0

Gnomad AFR AF: 0.0217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00359

Gnomad ASJ AF: 0.00469

Gnomad EAS AF: 0.00376

Gnomad SAS AF: 0.0159

Gnomad FIN AF: 0.000885

Gnomad MID AF: 0.0157

Gnomad NFE AF: 0.00498

Gnomad OTH AF: 0.00541

GnomAD4 exome AF: 0.00131 AC: 125 AN: 95360 Hom.: 0 AF XY: 0.00126 AC XY: 31 AN XY: 24524

African (AFR) AF: 0.00353 AC: 7 AN: 1984

American (AMR) AF: 0.00108 AC: 4 AN: 3719

Ashkenazi Jewish (ASJ) AF: 0.00100 AC: 3 AN: 2998

East Asian (EAS) AF: 0.000560 AC: 3 AN: 5359

South Asian (SAS) AF: 0.00113 AC: 6 AN: 5294

European-Finnish (FIN) AF: 0.00160 AC: 24 AN: 14965

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 605

European-Non Finnish (NFE) AF: 0.00122 AC: 69 AN: 56421

Other (OTH) AF: 0.00224 AC: 9 AN: 4015

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00939 AC: 819 AN: 87182 Hom.: 11 Cov.: 0 AF XY: 0.00657 AC XY: 106 AN XY: 16146

African (AFR) AF: 0.0216 AC: 504 AN: 23307

American (AMR) AF: 0.00358 AC: 27 AN: 7535

Ashkenazi Jewish (ASJ) AF: 0.00469 AC: 11 AN: 2344

East Asian (EAS) AF: 0.00378 AC: 11 AN: 2912

South Asian (SAS) AF: 0.0160 AC: 29 AN: 1809

European-Finnish (FIN) AF: 0.000885 AC: 2 AN: 2261

Middle Eastern (MID) AF: 0.0174 AC: 3 AN: 172

European-Non Finnish (NFE) AF: 0.00498 AC: 225 AN: 45138

Other (OTH) AF: 0.00621 AC: 7 AN: 1128

Alfa AF: 0.00 Hom.: 943

ClinVar

ClinVar submissions

Significance: Likely 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		-0.70
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;