chrX-77830970-T-TTTTTA

Position:

• chrX-77830970-T-TTTTTA

Variant summary

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

The NM_001367916.1(MAGT1):​c.902-76_902-75insTAAAA 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

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-T-TTTTTA is Benign according to our data. Variant chrX-77830970-T-TTTTTA is described in ClinVar as [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 55 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAGT1	NM_001367916.1	c.902-76_902-75insTAAAA		intron_variant		ENST00000618282.5	NP_001354845.1
MAGT1	NM_032121.5	c.998-76_998-75insTAAAA		intron_variant			NP_115497.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAGT1	ENST00000618282.5	c.902-76_902-75insTAAAA		intron_variant		1	NM_001367916.1	ENSP00000480732	P1

Frequencies

GnomAD3 genomes AF: 0.0275 AC: 2399 AN: 87175 Hom.: 55 Cov.: 0 AF XY: 0.0186 AC XY: 300 AN XY: 16131

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

Gnomad4 AFR exome AF: 0.00908

Gnomad4 AMR exome AF: 0.00323

Gnomad4 ASJ exome AF: 0.00434

Gnomad4 EAS exome AF: 0.00991

Gnomad4 SAS exome AF: 0.00189

Gnomad4 FIN exome AF: 0.00127

Gnomad4 NFE exome AF: 0.00408

Gnomad4 OTH exome AF: 0.00698

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

Gnomad4 AFR AF: 0.0481

Gnomad4 AMR AF: 0.0197

Gnomad4 ASJ AF: 0.0269

Gnomad4 EAS AF: 0.0450

Gnomad4 SAS AF: 0.0381

Gnomad4 FIN AF: 0.000885

Gnomad4 NFE AF: 0.0184

Gnomad4 OTH AF: 0.0196

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 28, 2020

- -

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;