Genetic Variant MIOX:p.Arg39Gly (chr22-50487680-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_017584.6(MIOX):c.115C>G(p.Arg39Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R39C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MIOX
NM_017584.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.29

Publications

1 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.833

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017584.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIOX	NM_017584.6	MANE Select	c.115C>G	p.Arg39Gly	missense	Exon 3 of 10	NP_060054.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIOX	ENST00000216075.11	TSL:1 MANE Select	c.115C>G	p.Arg39Gly	missense	Exon 3 of 10	ENSP00000216075.6	Q9UGB7-1
MIOX	ENST00000395732.7	TSL:1	c.115C>G	p.Arg39Gly	missense	Exon 3 of 10	ENSP00000379081.3	A6PVH2
MIOX	ENST00000395733.7	TSL:1	c.115C>G	p.Arg39Gly	missense	Exon 3 of 8	ENSP00000379082.3	Q9UGB7-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461256

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726930

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33400

American (AMR)

AF:

0.00

AC:

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53064

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111902

Other (OTH)

AF:

0.00

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.0000726

AC:

AN:

41334

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.28

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.015

MetaRNN

Pathogenic

0.83

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.9

PhyloP100

4.3

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-5.0

REVEL

Uncertain

0.37

Sift

Benign

0.068

Sift4G

Uncertain

0.019

Polyphen

0.99

Vest4

0.77

MutPred

0.78

Gain of catalytic residue at V40 (P = 0.0214)

MVP

0.17

MPC

0.35

ClinPred

0.99

GERP RS

4.4

PromoterAI

-0.0059

Neutral

(source)

Varity_R

0.57

gMVP

0.78

Mutation Taster

=6/94

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over