Genetic Variant MIOX:p.Arg39Cys (chr22-50487680-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017584.6(MIOX):c.115C>T(p.Arg39Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000694 in 1,613,468 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

MIOX
NM_017584.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.29

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]

MIOX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIOX	NM_017584.6 link	c.115C>T	p.Arg39Cys	missense_variant	Exon 3 of 10	ENST00000216075.11	NP_060054.4	Q9UGB7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MIOX	ENST00000216075.11 link	c.115C>T	p.Arg39Cys	missense_variant	Exon 3 of 10	1	NM_017584.6	ENSP00000216075.6	Q9UGB7-1
MIOX	ENST00000395732.7 link	c.115C>T	p.Arg39Cys	missense_variant	Exon 3 of 10	1		ENSP00000379081.3	A6PVH2
MIOX	ENST00000395733.7 link	c.115C>T	p.Arg39Cys	missense_variant	Exon 3 of 8	1		ENSP00000379082.3	Q9UGB7-2
MIOX	ENST00000451761.1 link	c.100C>T	p.Arg34Cys	missense_variant	Exon 2 of 9	3		ENSP00000409894.1	A6PVH4

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

250602

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135576

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.0000530

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000616

AC:

AN:

1461256

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

726930

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000728

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.000145

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000289

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:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000772

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.115C>T (p.R39C) alteration is located in exon 3 (coding exon 3) of the MIOX gene. This alteration results from a C to T substitution at nucleotide position 115, causing the arginine (R) at amino acid position 39 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

Uncertain

0.41

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.45

.;T;.;.

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

D;D;D;D

M_CAP

Benign

0.034

MetaRNN

Uncertain

0.70

D;D;D;D

MetaSVM

Uncertain

-0.076

MutationAssessor

Pathogenic

3.2

M;M;.;.

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-5.6

D;D;D;D

REVEL

Uncertain

0.45

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.76

MVP

0.23

MPC

0.38

ClinPred

0.98

GERP RS

4.4

Varity_R

0.52

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over