NM_001367916.1:c.992+45G>A

Variant names:

• chrX-77830760-C-T
• rs184963094
• NM_001367916.1:c.992+45G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001367916.1(MAGT1):​c.992+45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 711,725 control chromosomes in the GnomAD database, including 86 homozygotes. There are 2,788 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (9 hom., 360 hem., cov: 23)
  • Exomes 𝑓: 0.016 (77 hom. 2428 hem.)
• Consequence: MAGT1 NM_001367916.1 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.29
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant X-77830760-C-T is Benign according to our data. Variant chrX-77830760-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1216721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0114 (1252/110200) while in subpopulation NFE AF = 0.0184 (967/52676). AF 95% confidence interval is 0.0174. There are 9 homozygotes in GnomAd4. There are 360 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 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.992+45G>A		intron	N/A	NP_001354845.1	Q9H0U3-1
	MAGT1	NM_032121.5		c.1088+45G>A		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.992+45G>A		intron	N/A	ENSP00000480732.1	Q9H0U3-1
	MAGT1	ENST00000358075.11	TSL:1	c.992+45G>A		intron	N/A	ENSP00000354649.6	Q9H0U3-1
	MAGT1	ENST00000685015.1		c.902-3951G>A		intron	N/A	ENSP00000509969.1	A0A8I5QKX7

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1252 AN: 110166 Hom.: 9 Cov.: 23

Gnomad AFR AF: 0.00222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00906

Gnomad ASJ AF: 0.00381

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0163

Gnomad FIN AF: 0.00967

Gnomad MID AF: 0.00431

Gnomad NFE AF: 0.0184

Gnomad OTH AF: 0.0121

GnomAD2 exomes AF: 0.0115 AC: 1668 AN: 144901 AF XY: 0.0119

Gnomad AFR exome AF: 0.00189

Gnomad AMR exome AF: 0.00357

Gnomad ASJ exome AF: 0.00371

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00947

Gnomad NFE exome AF: 0.0176

Gnomad OTH exome AF: 0.0106

GnomAD4 exome AF: 0.0158 AC: 9513 AN: 601525 Hom.: 77 Cov.: 9 AF XY: 0.0154 AC XY: 2428 AN XY: 157199

African (AFR) AF: 0.00126 AC: 20 AN: 15921

American (AMR) AF: 0.00399 AC: 115 AN: 28809

Ashkenazi Jewish (ASJ) AF: 0.00316 AC: 44 AN: 13909

East Asian (EAS) AF: 0.0000835 AC: 2 AN: 23955

South Asian (SAS) AF: 0.0171 AC: 528 AN: 30800

European-Finnish (FIN) AF: 0.0107 AC: 376 AN: 35071

Middle Eastern (MID) AF: 0.0104 AC: 29 AN: 2786

European-Non Finnish (NFE) AF: 0.0191 AC: 8085 AN: 422880

Other (OTH) AF: 0.0115 AC: 314 AN: 27394

GnomAD4 genome AF: 0.0114 AC: 1252 AN: 110200 Hom.: 9 Cov.: 23 AF XY: 0.0110 AC XY: 360 AN XY: 32874

African (AFR) AF: 0.00221 AC: 68 AN: 30708

American (AMR) AF: 0.00905 AC: 93 AN: 10274

Ashkenazi Jewish (ASJ) AF: 0.00381 AC: 10 AN: 2627

East Asian (EAS) AF: 0.00 AC: 0 AN: 3550

South Asian (SAS) AF: 0.0164 AC: 44 AN: 2684

European-Finnish (FIN) AF: 0.00967 AC: 51 AN: 5276

Middle Eastern (MID) AF: 0.00474 AC: 1 AN: 211

European-Non Finnish (NFE) AF: 0.0184 AC: 967 AN: 52676

Other (OTH) AF: 0.0119 AC: 18 AN: 1510

Alfa AF: 0.0153 Hom.: 168

Bravo AF: 0.0110

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.38
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs184963094; hg19: chrX-77086257;