chrX-49166269-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_024859.4(MAGIX):​c.875C>T​(p.Pro292Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,194,708 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict 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: 24)
Exomes 𝑓: 0.000011 ( 0 hom. 9 hem. )

Consequence

MAGIX
NM_024859.4 missense

Scores

14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.882
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.05843997).
BS2
High Hemizygotes in GnomAdExome4 at 9 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAGIXNM_024859.4 linkc.875C>T p.Pro292Leu missense_variant Exon 6 of 6 ENST00000595224.6 NP_079135.3 Q9H6Y5-1
MAGIXNM_001395401.1 linkc.698C>T p.Pro233Leu missense_variant Exon 5 of 5 NP_001382330.1
MAGIXNM_001099681.2 linkc.647C>T p.Pro216Leu missense_variant Exon 5 of 5 NP_001093151.2 Q9H6Y5A0A087WUY6
MAGIXNM_001099682.2 linkc.632C>T p.Pro211Leu 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.875C>T p.Pro292Leu missense_variant Exon 6 of 6 5 NM_024859.4 ENSP00000471299.1 Q9H6Y5-1

Frequencies

GnomAD3 genomes
AF:
0.00000886
AC:
1
AN:
112907
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
35057
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000188
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000688
AC:
1
AN:
145401
Hom.:
0
AF XY:
0.0000221
AC XY:
1
AN XY:
45351
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000164
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000111
AC:
12
AN:
1081801
Hom.:
0
Cov.:
30
AF XY:
0.0000256
AC XY:
9
AN XY:
352221
show subpopulations
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:
0.0000120
Gnomad4 OTH exome
AF:
0.0000440
GnomAD4 genome
AF:
0.00000886
AC:
1
AN:
112907
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
35057
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000188
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000254
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 26, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.875C>T (p.P292L) alteration is located in exon 6 (coding exon 6) of the MAGIX gene. This alteration results from a C to T substitution at nucleotide position 875, causing the proline (P) at amino acid position 292 to be replaced by a leucine (L). 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
0.092
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
9.5
DANN
Benign
0.85
DEOGEN2
Benign
0.026
.;T;T;T;T
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.74
T;T;T;T;T
M_CAP
Benign
0.0071
T
MetaRNN
Benign
0.058
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
.;.;.;L;.
PrimateAI
Benign
0.45
T
Sift4G
Benign
0.61
T;T;T;T;T
Polyphen
0.0040
B;.;.;B;.
Vest4
0.057
MutPred
0.19
.;.;.;Loss of relative solvent accessibility (P = 0.0676);.;
MVP
0.18
ClinPred
0.053
T
GERP RS
2.6
Varity_R
0.040
gMVP
0.24

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: rs782818034; hg19: chrX-49022608; API