X-77856754-A-T

Variant names:

• chrX-77856754-A-T
• rs61732679
• NM_001367916.1:c.651T>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001367916.1(MAGT1):​c.651T>A​(p.Thr217Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00285 in 1,207,966 control chromosomes in the GnomAD database, including 51 homozygotes. There are 889 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (27 hom., 430 hem., cov: 23)
  • Exomes 𝑓: 0.0016 (24 hom. 459 hem.)
• Consequence: MAGT1 NM_001367916.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.35

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant X-77856754-A-T is Benign according to our data. Variant chrX-77856754-A-T is described in ClinVar as [Benign]. Clinvar id is 129568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.35 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.015 (1678/111891) while in subpopulation AFR AF= 0.0514 (1587/30856). AF 95% confidence interval is 0.0493. There are 27 homozygotes in gnomad4. There are 430 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 27 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGT1	NM_001367916.1	c.651T>A	p.Thr217Thr	synonymous_variant	Exon 5 of 10	ENST00000618282.5	NP_001354845.1
MAGT1	NM_032121.5	c.747T>A	p.Thr249Thr	synonymous_variant	Exon 5 of 10		NP_115497.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGT1	ENST00000618282.5	c.651T>A	p.Thr217Thr	synonymous_variant	Exon 5 of 10	1	NM_001367916.1	ENSP00000480732.1

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 1676 AN: 111837 Hom.: 27 Cov.: 23 AF XY: 0.0126 AC XY: 429 AN XY: 34027

Gnomad AFR AF: 0.0515

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.00415

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000370

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000169

Gnomad OTH AF: 0.0161

GnomAD3 exomes AF: 0.00449 AC: 820 AN: 182455 Hom.: 12 AF XY: 0.00268 AC XY: 180 AN XY: 67165

Gnomad AFR exome AF: 0.0534

Gnomad AMR exome AF: 0.00289

Gnomad ASJ exome AF: 0.00308

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000322

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000857

Gnomad OTH exome AF: 0.00200

GnomAD4 exome AF: 0.00161 AC: 1770 AN: 1096075 Hom.: 24 Cov.: 28 AF XY: 0.00127 AC XY: 459 AN XY: 361585

Gnomad4 AFR exome AF: 0.0513

Gnomad4 AMR exome AF: 0.00330

Gnomad4 ASJ exome AF: 0.00331

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000278

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000523

Gnomad4 OTH exome AF: 0.00380

GnomAD4 genome AF: 0.0150 AC: 1678 AN: 111891 Hom.: 27 Cov.: 23 AF XY: 0.0126 AC XY: 430 AN XY: 34091

Gnomad4 AFR AF: 0.0514

Gnomad4 AMR AF: 0.00451

Gnomad4 ASJ AF: 0.00415

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000169

Gnomad4 OTH AF: 0.0159

Alfa AF: 0.00844 Hom.: 35

Bravo AF: 0.0171

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 06, 2021	- -

not specified Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

-

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 02, 2025

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs61732679; hg19: chrX-77112251;