X-49163882-C-A

Variant names:

• chrX-49163882-C-A
• rs2065346924
• NM_024859.4:c.149C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024859.4(MAGIX):​c.149C>A​(p.Ala50Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: MAGIX NM_024859.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.767

Genes affected

MAGIX (HGNC:30006): (MAGI family member, X-linked)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26926386).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGIX	NM_024859.4	c.149C>A	p.Ala50Glu	missense_variant	Exon 2 of 6	ENST00000595224.6	NP_079135.3
MAGIX	NM_001099681.2	c.149C>A	p.Ala50Glu	missense_variant	Exon 2 of 5		NP_001093151.2
MAGIX	NM_001099682.2	c.149C>A	p.Ala50Glu	missense_variant	Exon 2 of 5		NP_001093152.2
MAGIX	NM_001395401.1	c.-102C>A		5_prime_UTR_variant	Exon 2 of 5		NP_001382330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAGIX	ENST00000595224.6	c.149C>A	p.Ala50Glu	missense_variant	Exon 2 of 6	5	NM_024859.4	ENSP00000471299.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 920004 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 287634

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.149C>A (p.A50E) alteration is located in exon 2 (coding exon 2) of the MAGIX gene. This alteration results from a C to A substitution at nucleotide position 149, causing the alanine (A) at amino acid position 50 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.92
DEOGEN2	Benign	0.040	T;T;T
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.61	T;T;T
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	.;.;L
PrimateAI	Pathogenic	0.83	D
Sift4G	Uncertain	0.020	D;D;D
Polyphen		1.0	.;.;D
Vest4		0.26
MutPred		0.40		Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);
MVP		0.23
ClinPred		0.64	D
GERP RS		3.4
Varity_R		0.26
gMVP		0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs2065346924; hg19: chrX-49020220;