X-49165298-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_024859.4(MAGIX):​c.616C>T​(p.Arg206Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,180,852 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R206H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., 4 hem., cov: 24)
Exomes 𝑓: 0.000020 ( 0 hom. 5 hem. )

Consequence

MAGIX
NM_024859.4 missense

Scores

1
3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.00
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 -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.26924768).
BS2
High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAGIXNM_024859.4 linkc.616C>T p.Arg206Cys missense_variant Exon 5 of 6 ENST00000595224.6 NP_079135.3 Q9H6Y5-1
MAGIXNM_001395401.1 linkc.439C>T p.Arg147Cys missense_variant Exon 4 of 5 NP_001382330.1
MAGIXNM_001099681.2 linkc.388C>T p.Arg130Cys missense_variant Exon 4 of 5 NP_001093151.2 Q9H6Y5A0A087WUY6
MAGIXNM_001099682.2 linkc.388C>T p.Arg130Cys missense_variant Exon 4 of 5 NP_001093152.2 Q9H6Y5A0A087X263

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAGIXENST00000595224.6 linkc.616C>T p.Arg206Cys missense_variant Exon 5 of 6 5 NM_024859.4 ENSP00000471299.1 Q9H6Y5-1

Frequencies

GnomAD3 genomes
AF:
0.0000802
AC:
9
AN:
112288
Hom.:
0
Cov.:
24
AF XY:
0.000116
AC XY:
4
AN XY:
34460
show subpopulations
Gnomad AFR
AF:
0.0000324
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000941
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:
0.0000752
Gnomad OTH
AF:
0.00199
GnomAD3 exomes
AF:
0.00000763
AC:
1
AN:
131041
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
40197
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000102
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000197
AC:
21
AN:
1068564
Hom.:
0
Cov.:
31
AF XY:
0.0000144
AC XY:
5
AN XY:
346594
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000330
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000353
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000169
Gnomad4 OTH exome
AF:
0.000111
GnomAD4 genome
AF:
0.0000802
AC:
9
AN:
112288
Hom.:
0
Cov.:
24
AF XY:
0.000116
AC XY:
4
AN XY:
34460
show subpopulations
Gnomad4 AFR
AF:
0.0000324
Gnomad4 AMR
AF:
0.0000941
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000752
Gnomad4 OTH
AF:
0.00199
Bravo
AF:
0.000121
ExAC
AF:
0.0000342
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 02, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.616C>T (p.R206C) alteration is located in exon 5 (coding exon 5) of the MAGIX gene. This alteration results from a C to T substitution at nucleotide position 616, causing the arginine (R) at amino acid position 206 to be replaced by a cysteine (C). 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
0.090
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
0.91
DANN
Benign
0.94
DEOGEN2
Benign
0.087
.;T;T;T;T;T
FATHMM_MKL
Benign
0.038
N
LIST_S2
Benign
0.74
T;T;T;T;T;T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.27
T;T;T;T;T;T
MetaSVM
Benign
-0.82
T
MutationAssessor
Pathogenic
3.0
.;.;.;M;.;.
PrimateAI
Benign
0.28
T
PROVEAN
Uncertain
-3.9
.;.;.;.;.;D
REVEL
Benign
0.096
Sift
Uncertain
0.0010
.;.;.;.;.;D
Sift4G
Uncertain
0.022
D;D;D;D;D;D
Polyphen
0.025
B;.;.;B;.;B
Vest4
0.076
MutPred
0.54
.;.;.;Loss of MoRF binding (P = 0.0031);.;.;
MVP
0.20
ClinPred
0.48
T
GERP RS
-4.1
Varity_R
0.11
gMVP
0.74

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs782468533; hg19: chrX-49021636; COSMIC: COSV66256544; COSMIC: COSV66256544; API