X-77841311-A-C

Variant names:

• chrX-77841311-A-C
• rs137852222
• NM_001367916.1:c.836T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001367916.1(MAGT1):​c.836T>G​(p.Val279Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 22)
• Consequence: MAGT1 NM_001367916.1 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 6.34
• 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: Unknown, XL Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.87

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGT1	NM_001367916.1	c.836T>G	p.Val279Gly	missense_variant	Exon 8 of 10	ENST00000618282.5	NP_001354845.1
MAGT1	NM_032121.5	c.932T>G	p.Val311Gly	missense_variant	Exon 8 of 10		NP_115497.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGT1	ENST00000618282.5	c.836T>G	p.Val279Gly	missense_variant	Exon 8 of 10	1	NM_001367916.1	ENSP00000480732.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Aug 08, 2013

OMIM

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.42	T;T;T
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	.;D;D
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Uncertain	0.16	D
MutationAssessor	Uncertain	2.5	.;.;M
PhyloP100		6.3
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.3	D;.;.
REVEL	Pathogenic	0.71
Sift	Uncertain	0.0010	D;.;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.98	.;.;D
Vest4		0.66
MutPred		0.79		.;.;Loss of stability (P = 0.0653);
MVP		0.84
MPC		1.2
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.83
gMVP		0.99
Mutation Taster		=32/68	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs137852222; hg19: chrX-77096808;