chrX-77830970-TTTTTATTTTATTTTA-T

Position:

• chrX-77830970-TTTTTATTTTATTTTA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001367916.1(MAGT1):​c.902-90_902-76del 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. 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

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 1228783.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome 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 gnomad4_exome. There are 555 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 38 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGT1	NM_001367916.1	c.902-90_902-76del		intron_variant		ENST00000618282.5	NP_001354845.1
MAGT1	NM_032121.5	c.998-90_998-76del		intron_variant			NP_115497.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGT1	ENST00000618282.5	c.902-90_902-76del		intron_variant		1	NM_001367916.1	ENSP00000480732	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 6338 AN: 87126 Hom.: 260 Cov.: 0 AF XY: 0.0607 AC XY: 977 AN XY: 16098 FAILED QC

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

Gnomad4 AFR exome AF: 0.0314

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.00836

Gnomad4 EAS exome AF: 0.0101

Gnomad4 SAS exome AF: 0.00151

Gnomad4 FIN exome AF: 0.0188

Gnomad4 NFE exome AF: 0.0226

Gnomad4 OTH exome AF: 0.0227

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

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0464

Gnomad4 ASJ AF: 0.0375

Gnomad4 EAS AF: 0.0536

Gnomad4 SAS AF: 0.0227

Gnomad4 FIN AF: 0.0208

Gnomad4 NFE AF: 0.0652

Gnomad4 OTH AF: 0.0764

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 06, 2020

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201564456; hg19: chrX-77086467;