X-49166248-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_024859.4(MAGIX):​c.854C>G​(p.Pro285Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000833 in 1,200,812 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. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.0000074 ( 0 hom. 2 hem. )

Consequence

MAGIX
NM_024859.4 missense

Scores

2
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.359
Variant links:
Genes affected
MAGIX (HGNC:30006): (MAGI family member, X-linked)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.08831784).
BS2
High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAGIXNM_024859.4 linkc.854C>G p.Pro285Arg missense_variant Exon 6 of 6 ENST00000595224.6 NP_079135.3 Q9H6Y5-1
MAGIXNM_001395401.1 linkc.677C>G p.Pro226Arg missense_variant Exon 5 of 5 NP_001382330.1
MAGIXNM_001099681.2 linkc.626C>G p.Pro209Arg missense_variant Exon 5 of 5 NP_001093151.2 Q9H6Y5A0A087WUY6
MAGIXNM_001099682.2 linkc.611C>G p.Pro204Arg missense_variant Exon 5 of 5 NP_001093152.2 Q9H6Y5A0A087X263

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAGIXENST00000595224.6 linkc.854C>G p.Pro285Arg missense_variant Exon 6 of 6 5 NM_024859.4 ENSP00000471299.1 Q9H6Y5-1

Frequencies

GnomAD3 genomes
AF:
0.00000886
AC:
1
AN:
112815
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34957
show subpopulations
Gnomad AFR
AF:
0.0000322
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00000735
AC:
8
AN:
1087945
Hom.:
0
Cov.:
31
AF XY:
0.00000563
AC XY:
2
AN XY:
355555
show subpopulations
Gnomad4 AFR exome
AF:
0.0000764
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:
0.000131
GnomAD4 genome
AF:
0.0000177
AC:
2
AN:
112867
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
35019
show subpopulations
Gnomad4 AFR
AF:
0.0000642
Gnomad4 AMR
AF:
0.00
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:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.854C>G (p.P285R) alteration is located in exon 6 (coding exon 6) of the MAGIX gene. This alteration results from a C to G substitution at nucleotide position 854, causing the proline (P) at amino acid position 285 to be replaced by an arginine (R). 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
0.077
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.92
CADD
Benign
12
DANN
Uncertain
0.99
DEOGEN2
Benign
0.030
.;T;T;T;T
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.71
T;T;T;T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.088
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
.;.;.;L;.
PrimateAI
Benign
0.33
T
Sift4G
Uncertain
0.058
T;T;T;T;T
Polyphen
0.89
P;.;.;P;.
Vest4
0.035
MutPred
0.16
.;.;.;Loss of catalytic residue at P284 (P = 0.0191);.;
MVP
0.095
ClinPred
0.80
D
GERP RS
0.48
Varity_R
0.048
gMVP
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs782164364; hg19: chrX-49022587; API