X-77830970-TTTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTA-TTTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTA

Variant names:

• chrX-77830970-T-TTTTTATTTTATTTTATTTTATTTTA
• rs201564456
• NM_001367916.1:c.902-100_902-76dupTAAAATAAAATAAAATAAAATAAAA

Variant summary

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

The NM_001367916.1(MAGT1):​c.902-100_902-76dupTAAAATAAAATAAAATAAAATAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_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 0.00080 (0 hom., 4 hem., cov: 0)
  • Exomes 𝑓: 0.00024 (0 hom. 2 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAGT1 NM_001367916.1 intron
• Clinical Significance: Not reported in ClinVar
• 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 -4 ACMG points.

• BS2: High Hemizygotes in GnomAd4 at 4 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.902-100_902-76dupTAAAATAAAATAAAATAAAATAAAA		intron	N/A	NP_001354845.1	Q9H0U3-1
	MAGT1	NM_032121.5		c.998-100_998-76dupTAAAATAAAATAAAATAAAATAAAA		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_902-75insTAAAATAAAATAAAATAAAATAAAA		intron	N/A	ENSP00000480732.1	Q9H0U3-1
	MAGT1	ENST00000358075.11	TSL:1	c.902-76_902-75insTAAAATAAAATAAAATAAAATAAAA		intron	N/A	ENSP00000354649.6	Q9H0U3-1
	MAGT1	ENST00000685015.1		c.902-4162_902-4161insTAAAATAAAATAAAATAAAATAAAA		intron	N/A	ENSP00000509969.1	A0A8I5QKX7

Frequencies

GnomAD3 genomes AF: 0.000803 AC: 70 AN: 87205 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000266

Gnomad ASJ AF: 0.000426

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00128

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000241 AC: 23 AN: 95366 Hom.: 0 AF XY: 0.0000815 AC XY: 2 AN XY: 24526

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

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2998

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 5294

European-Finnish (FIN) AF: 0.000334 AC: 5 AN: 14965

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

European-Non Finnish (NFE) AF: 0.000301 AC: 17 AN: 56427

Other (OTH) AF: 0.000249 AC: 1 AN: 4015

GnomAD4 genome AF: 0.000803 AC: 70 AN: 87202 Hom.: 0 Cov.: 0 AF XY: 0.000248 AC XY: 4 AN XY: 16148

African (AFR) AF: 0.000386 AC: 9 AN: 23321

American (AMR) AF: 0.000265 AC: 2 AN: 7535

Ashkenazi Jewish (ASJ) AF: 0.000426 AC: 1 AN: 2346

East Asian (EAS) AF: 0.00 AC: 0 AN: 2914

South Asian (SAS) AF: 0.00 AC: 0 AN: 1809

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2261

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

European-Non Finnish (NFE) AF: 0.00128 AC: 58 AN: 45140

Other (OTH) AF: 0.00 AC: 0 AN: 1128

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.70

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;