X-77895449-G-C

Variant names:

• chrX-77895449-G-C
• ENST00000358075.11:c.-39C>G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_032121.5(MAGT1):​c.58C>G​(p.Arg20Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,086,790 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000028 (0 hom. 2 hem.)
• Consequence: MAGT1 NM_032121.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.466

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06621328).
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGT1	NM_032121.5	c.58C>G	p.Arg20Gly	missense_variant	Exon 1 of 10		NP_115497.4
MAGT1	NM_001367916.1	c.-39C>G		upstream_gene_variant		ENST00000618282.5	NP_001354845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGT1	ENST00000618282.5	c.-39C>G		upstream_gene_variant		1	NM_001367916.1	ENSP00000480732.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000276 AC: 3 AN: 1086790 Hom.: 0 Cov.: 31 AF XY: 0.00000564 AC XY: 2 AN XY: 354612

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000239

Gnomad4 OTH exome AF: 0.0000219

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.9
DANN	Benign	0.75
DEOGEN2	Benign	0.095	T;T
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.33	.;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.066	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.22	N;.
REVEL	Benign	0.029
Sift	Benign	0.27	T;.
Sift4G	Benign	0.12	T;T
Vest4		0.069
MutPred		0.21		Loss of MoRF binding (P = 0.011);Loss of MoRF binding (P = 0.011);
MVP		0.093
MPC		0.61
ClinPred		0.049	T
GERP RS		0.91
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-77150946;