chrX-77895449-G-C

Variant names:

• chrX-77895449-G-C
• rs370329684
• ENST00000358075.11:c.-39C>G

Variant summary

Our verdict is Benign. The variant received -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. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R20W) has been classified as Likely benign.

• 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
• 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 -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032121.5. 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_032121.5		c.58C>G	p.Arg20Gly	missense	Exon 1 of 10	NP_115497.4	Q9H0U3
	MAGT1	NM_001367916.1	MANE Select	c.-39C>G		upstream_gene	N/A	NP_001354845.1	Q9H0U3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGT1	ENST00000358075.11	TSL:1	c.-39C>G		5_prime_UTR	Exon 1 of 10	ENSP00000354649.6	Q9H0U3-1
	MAGT1	ENST00000944450.1		c.-39C>G		5_prime_UTR	Exon 1 of 9	ENSP00000614509.1
	MAGT1	ENST00000691993.1		n.58C>G		non_coding_transcript_exon	Exon 1 of 11	ENSP00000509067.1	A0A087WU53

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

African (AFR) AF: 0.00 AC: 0 AN: 26180

American (AMR) AF: 0.00 AC: 0 AN: 33803

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19165

East Asian (EAS) AF: 0.00 AC: 0 AN: 29697

South Asian (SAS) AF: 0.00 AC: 0 AN: 52746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39891

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4121

European-Non Finnish (NFE) AF: 0.00000239 AC: 2 AN: 835557

Other (OTH) AF: 0.0000219 AC: 1 AN: 45630

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.9
DANN	Benign	0.75
DEOGEN2	Benign	0.095	T
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.47
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.029
Sift	Benign	0.27	T
Sift4G	Benign	0.12	T
Vest4		0.069
MutPred		0.21		Loss of MoRF binding (P = 0.011)
MVP		0.093
MPC		0.61
ClinPred		0.049	T
GERP RS		0.91
PromoterAI		-0.18	Neutral
gMVP		0.17
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs370329684; hg19: chrX-77150946;