X-77830970-TTTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTA-TTTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTATTTTA

Variant names:

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

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.902-80_902-76dupTAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 182,481 control chromosomes in the GnomAD database, including 58 homozygotes. There are 357 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (55 hom., 299 hem., cov: 0)
  • Exomes 𝑓: 0.0040 (3 hom. 58 hem.)
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant X-77830970-T-TTTTTA is Benign according to our data. Variant chrX-77830970-T-TTTTTA is described in ClinVar as Likely_benign. ClinVar VariationId is 1203711.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0275 (2397/87172) while in subpopulation AFR AF = 0.0481 (1121/23309). AF 95% confidence interval is 0.0458. There are 55 homozygotes in GnomAd4. There are 299 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 55 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.902-80_902-76dupTAAAA		intron	N/A	NP_001354845.1	Q9H0U3-1
	MAGT1	NM_032121.5		c.998-80_998-76dupTAAAA		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_902-75insTAAAA		intron	N/A	ENSP00000480732.1	Q9H0U3-1
	MAGT1	ENST00000358075.11	TSL:1	c.902-76_902-75insTAAAA		intron	N/A	ENSP00000354649.6	Q9H0U3-1
	MAGT1	ENST00000685015.1		c.902-4162_902-4161insTAAAA		intron	N/A	ENSP00000509969.1	A0A8I5QKX7

Frequencies

GnomAD3 genomes AF: 0.0275 AC: 2399 AN: 87175 Hom.: 55 Cov.: 0

Gnomad AFR AF: 0.0482

Gnomad AMI AF: 0.00694

Gnomad AMR AF: 0.0197

Gnomad ASJ AF: 0.0269

Gnomad EAS AF: 0.0448

Gnomad SAS AF: 0.0384

Gnomad FIN AF: 0.000885

Gnomad MID AF: 0.0471

Gnomad NFE AF: 0.0184

Gnomad OTH AF: 0.0190

GnomAD4 exome AF: 0.00403 AC: 384 AN: 95309 Hom.: 3 AF XY: 0.00237 AC XY: 58 AN XY: 24485

African (AFR) AF: 0.00908 AC: 18 AN: 1982

American (AMR) AF: 0.00323 AC: 12 AN: 3717

Ashkenazi Jewish (ASJ) AF: 0.00434 AC: 13 AN: 2995

East Asian (EAS) AF: 0.00991 AC: 53 AN: 5349

South Asian (SAS) AF: 0.00189 AC: 10 AN: 5292

European-Finnish (FIN) AF: 0.00127 AC: 19 AN: 14963

Middle Eastern (MID) AF: 0.00166 AC: 1 AN: 604

European-Non Finnish (NFE) AF: 0.00408 AC: 230 AN: 56395

Other (OTH) AF: 0.00698 AC: 28 AN: 4012

GnomAD4 genome AF: 0.0275 AC: 2397 AN: 87172 Hom.: 55 Cov.: 0 AF XY: 0.0185 AC XY: 299 AN XY: 16140

African (AFR) AF: 0.0481 AC: 1121 AN: 23309

American (AMR) AF: 0.0197 AC: 148 AN: 7531

Ashkenazi Jewish (ASJ) AF: 0.0269 AC: 63 AN: 2346

East Asian (EAS) AF: 0.0450 AC: 131 AN: 2909

South Asian (SAS) AF: 0.0381 AC: 69 AN: 1809

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

Middle Eastern (MID) AF: 0.0465 AC: 8 AN: 172

European-Non Finnish (NFE) AF: 0.0184 AC: 829 AN: 45135

Other (OTH) AF: 0.0196 AC: 22 AN: 1124

Alfa AF: 0.00544 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 (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;