22-50487968-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_017584.6(MIOX):​c.260C>T​(p.Ser87Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000266 in 1,613,876 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 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

MIOX
NM_017584.6 missense

Scores

7
9
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.94
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 Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.769

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MIOXNM_017584.6 linkc.260C>T p.Ser87Leu missense_variant Exon 4 of 10 ENST00000216075.11 NP_060054.4 Q9UGB7-1
MIOXXM_005261925.5 linkc.122C>T p.Ser41Leu missense_variant Exon 3 of 9 XP_005261982.1
MIOXXM_011530705.3 linkc.260C>T p.Ser87Leu missense_variant Exon 4 of 6 XP_011529007.1
MIOXXM_047441443.1 linkc.260C>T p.Ser87Leu 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.260C>T p.Ser87Leu missense_variant Exon 4 of 10 1 NM_017584.6 ENSP00000216075.6 Q9UGB7-1
MIOXENST00000395732.7 linkc.260C>T p.Ser87Leu missense_variant Exon 4 of 10 1 ENSP00000379081.3 A6PVH2
MIOXENST00000395733.7 linkc.260C>T p.Ser87Leu missense_variant Exon 4 of 8 1 ENSP00000379082.3 Q9UGB7-2
MIOXENST00000451761.1 linkc.245C>T p.Ser82Leu missense_variant Exon 3 of 9 3 ENSP00000409894.1 A6PVH4

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152186
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000319
AC:
8
AN:
250996
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135768
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000265
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000274
AC:
40
AN:
1461690
Hom.:
0
Cov.:
33
AF XY:
0.0000316
AC XY:
23
AN XY:
727144
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000279
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152186
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.0000147
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000381
Hom.:
0
Bravo
AF:
0.0000491
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000659
AC:
8
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 12, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.260C>T (p.S87L) 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 260, causing the serine (S) at amino acid position 87 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
Pathogenic
0.96
BayesDel_addAF
Benign
0.0079
T
BayesDel_noAF
Uncertain
0.050
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.63
.;D;.;.
Eigen
Pathogenic
0.69
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Pathogenic
0.98
D;D;D;D
M_CAP
Benign
0.060
D
MetaRNN
Pathogenic
0.77
D;D;D;D
MetaSVM
Uncertain
0.34
D
MutationAssessor
Pathogenic
3.5
H;H;.;.
PrimateAI
Uncertain
0.62
T
PROVEAN
Pathogenic
-5.9
D;D;D;D
REVEL
Uncertain
0.43
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Uncertain
0.014
D;D;D;D
Polyphen
1.0
D;D;D;.
Vest4
0.82
MVP
0.25
MPC
0.34
ClinPred
0.92
D
GERP RS
4.4
Varity_R
0.83
gMVP
0.72

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs201562892; hg19: chr22-50926397; API