chrX-77830839-T-C

Variant names:

• chrX-77830839-T-C
• rs2076895484
• NM_001367916.1:c.958A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367916.1(MAGT1):​c.958A>G​(p.Ile320Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAGT1 NM_001367916.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18371752).

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.958A>G	p.Ile320Val	missense	Exon 9 of 10	NP_001354845.1	Q9H0U3-1
	MAGT1	NM_032121.5		c.1054A>G	p.Ile352Val	missense	Exon 9 of 10	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.958A>G	p.Ile320Val	missense	Exon 9 of 10	ENSP00000480732.1	Q9H0U3-1
	MAGT1	ENST00000358075.11	TSL:1	c.958A>G	p.Ile320Val	missense	Exon 9 of 10	ENSP00000354649.6	Q9H0U3-1
	MAGT1	ENST00000688650.1		c.868A>G	p.Ile290Val	missense	Exon 8 of 9	ENSP00000509785.1	A0A8I5KYH1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1048714 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 330194

African (AFR) AF: 0.00 AC: 0 AN: 25058

American (AMR) AF: 0.00 AC: 0 AN: 33199

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18184

East Asian (EAS) AF: 0.00 AC: 0 AN: 28290

South Asian (SAS) AF: 0.00 AC: 0 AN: 48108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38589

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3928

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 809793

Other (OTH) AF: 0.00 AC: 0 AN: 43565

GnomAD4 genome Cov.: 22

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	15
DANN	Benign	0.74
DEOGEN2	Benign	0.094	T
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.91	N
PhyloP100		1.4
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.035
Sift	Benign	0.48	T
Sift4G	Benign	0.72	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.46		Gain of methylation at R322 (P = 0.1061)
MVP		0.20
MPC		0.39
ClinPred		0.16	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.73
Mutation Taster		=94/6	polymorphism

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: rs2076895484; hg19: chrX-77086336;