chrX-49163818-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.85C>G​(p.Arg29Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000191 in 1,047,863 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000062 ( 0 hom., 2 hem., cov: 23)
Exomes 𝑓: 0.000014 ( 0 hom. 4 hem. )

Consequence

MAGIX
NM_024859.4 missense

Scores

1
3
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.101
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=0.1881156).
BS2
High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAGIXNM_024859.4 linkc.85C>G p.Arg29Gly missense_variant Exon 2 of 6 ENST00000595224.6 NP_079135.3 Q9H6Y5-1
MAGIXNM_001099681.2 linkc.85C>G p.Arg29Gly missense_variant Exon 2 of 5 NP_001093151.2 Q9H6Y5A0A087WUY6
MAGIXNM_001099682.2 linkc.85C>G p.Arg29Gly missense_variant Exon 2 of 5 NP_001093152.2 Q9H6Y5A0A087X263
MAGIXNM_001395401.1 linkc.-166C>G 5_prime_UTR_variant Exon 2 of 5 NP_001382330.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAGIXENST00000595224.6 linkc.85C>G p.Arg29Gly missense_variant Exon 2 of 6 5 NM_024859.4 ENSP00000471299.1 Q9H6Y5-1

Frequencies

GnomAD3 genomes
AF:
0.0000621
AC:
7
AN:
112632
Hom.:
0
Cov.:
23
AF XY:
0.0000573
AC XY:
2
AN XY:
34890
show subpopulations
Gnomad AFR
AF:
0.000225
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:
0.0000139
AC:
13
AN:
935231
Hom.:
0
Cov.:
29
AF XY:
0.0000136
AC XY:
4
AN XY:
294349
show subpopulations
Gnomad4 AFR exome
AF:
0.000159
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:
0.0000130
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000621
AC:
7
AN:
112632
Hom.:
0
Cov.:
23
AF XY:
0.0000573
AC XY:
2
AN XY:
34890
show subpopulations
Gnomad4 AFR
AF:
0.000225
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:
0.0000642

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 05, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.85C>G (p.R29G) alteration is located in exon 2 (coding exon 2) of the MAGIX gene. This alteration results from a C to G substitution at nucleotide position 85, causing the arginine (R) at amino acid position 29 to be replaced by a glycine (G). 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
0.12
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
15
DANN
Uncertain
0.98
DEOGEN2
Benign
0.052
T;T;T
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.73
T;T;T
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.19
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
.;.;L
PrimateAI
Pathogenic
0.84
D
Sift4G
Uncertain
0.0060
D;D;D
Polyphen
0.99
.;.;D
Vest4
0.23
MutPred
0.47
Loss of MoRF binding (P = 0.0082);Loss of MoRF binding (P = 0.0082);Loss of MoRF binding (P = 0.0082);
MVP
0.12
ClinPred
0.87
D
GERP RS
0.36
Varity_R
0.14
gMVP
0.50

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.

Other links and lift over

dbSNP: rs1369646179; hg19: chrX-49020156; API