22-50488027-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_017584.6(MIOX):​c.319C>T​(p.Arg107Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000285 in 1,613,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

MIOX
NM_017584.6 missense

Scores

13
4
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.99
Variant links:
Genes affected
MIOX (HGNC:14522): (myo-inositol oxygenase) Enables ferric iron binding activity and inositol oxygenase activity. Involved in inositol catabolic process. Predicted to be located in cytoplasm and inclusion body. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.969

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MIOXNM_017584.6 linkc.319C>T p.Arg107Trp missense_variant Exon 4 of 10 ENST00000216075.11 NP_060054.4 Q9UGB7-1
MIOXXM_005261925.5 linkc.181C>T p.Arg61Trp missense_variant Exon 3 of 9 XP_005261982.1
MIOXXM_011530705.3 linkc.319C>T p.Arg107Trp missense_variant Exon 4 of 6 XP_011529007.1
MIOXXM_047441443.1 linkc.319C>T p.Arg107Trp missense_variant Exon 4 of 9 XP_047297399.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MIOXENST00000216075.11 linkc.319C>T p.Arg107Trp missense_variant Exon 4 of 10 1 NM_017584.6 ENSP00000216075.6 Q9UGB7-1
MIOXENST00000395732.7 linkc.319C>T p.Arg107Trp missense_variant Exon 4 of 10 1 ENSP00000379081.3 A6PVH2
MIOXENST00000395733.7 linkc.319C>T p.Arg107Trp missense_variant Exon 4 of 8 1 ENSP00000379082.3 Q9UGB7-2
MIOXENST00000451761.1 linkc.304C>T p.Arg102Trp missense_variant Exon 3 of 9 3 ENSP00000409894.1 A6PVH4

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152218
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000578
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000599
AC:
15
AN:
250372
Hom.:
0
AF XY:
0.0000590
AC XY:
8
AN XY:
135574
show subpopulations
Gnomad AFR exome
AF:
0.0000617
Gnomad AMR exome
AF:
0.0000579
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000381
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000266
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000253
AC:
37
AN:
1461424
Hom.:
0
Cov.:
33
AF XY:
0.0000275
AC XY:
20
AN XY:
727014
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000895
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152336
Hom.:
0
Cov.:
33
AF XY:
0.0000806
AC XY:
6
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000579
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000741
AC:
9
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 04, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.319C>T (p.R107W) alteration is located in exon 4 (coding exon 4) of the MIOX gene. This alteration results from a C to T substitution at nucleotide position 319, causing the arginine (R) at amino acid position 107 to be replaced by a tryptophan (W). 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
Pathogenic
0.76
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Pathogenic
0.42
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.63
.;D;.;.
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Pathogenic
0.99
D;D;D;D
M_CAP
Benign
0.071
D
MetaRNN
Pathogenic
0.97
D;D;D;D
MetaSVM
Uncertain
0.33
D
MutationAssessor
Pathogenic
3.5
H;H;.;.
PrimateAI
Uncertain
0.70
T
PROVEAN
Pathogenic
-8.0
D;D;D;D
REVEL
Pathogenic
0.73
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
1.0
D;D;D;.
Vest4
0.81
MutPred
0.93
Loss of disorder (P = 0.0148);Loss of disorder (P = 0.0148);Loss of disorder (P = 0.0148);.;
MVP
0.26
MPC
0.36
ClinPred
0.81
D
GERP RS
4.2
Varity_R
0.93
gMVP
0.87

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: rs377169234; hg19: chr22-50926456; API