Genetic Variant MAGIX:p.Ala28Asp (chrX-49163816-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024859.4(MAGIX):c.83C>A(p.Ala28Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000382 in 1,046,582 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000032 ( 0 hom. 0 hem. )

Consequence

MAGIX
NM_024859.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.08

Variant links:

Genes affected

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

MAGIX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23839948).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAGIX	NM_024859.4 link	c.83C>A	p.Ala28Asp	missense_variant	Exon 2 of 6	ENST00000595224.6	NP_079135.3	Q9H6Y5-1
MAGIX	NM_001099681.2 link	c.83C>A	p.Ala28Asp	missense_variant	Exon 2 of 5		NP_001093151.2	Q9H6Y5A0A087WUY6
MAGIX	NM_001099682.2 link	c.83C>A	p.Ala28Asp	missense_variant	Exon 2 of 5		NP_001093152.2	Q9H6Y5A0A087X263
MAGIX	NM_001395401.1 link	c.-168C>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 link	c.83C>A	p.Ala28Asp	missense_variant	Exon 2 of 6	5	NM_024859.4	ENSP00000471299.1		Q9H6Y5-1

Frequencies

GnomAD3 genomes

AF:

0.00000888

AC:

AN:

112637

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34893

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000928

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000321

AC:

AN:

933945

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

293715

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000320

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

AF:

0.00000888

AC:

AN:

112637

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34893

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000928

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 02, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.83C>A (p.A28D) 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 83, causing the alanine (A) at amino acid position 28 to be replaced by an aspartic acid (D). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.059

T;T;T

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.66

T;T;T

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;.;L

PrimateAI

Pathogenic

0.86

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

0.76

.;.;P

Vest4

0.31

MutPred

0.32

Loss of MoRF binding (P = 0.019);Loss of MoRF binding (P = 0.019);Loss of MoRF binding (P = 0.019);

MVP

0.13

ClinPred

0.83

GERP RS

3.1

Varity_R

0.14

gMVP

0.26

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over