Genetic Variant MIOX:p.Arg29Gln (chr22-50487455-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1BP4_StrongBS2

The NM_017584.6(MIOX):c.86G>A(p.Arg29Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000149 in 1,613,636 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 2 hom. )

Consequence

MIOX
NM_017584.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.54

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 Likely_benign. Variant got -6 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity MIOX_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.044394344).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIOX	NM_017584.6 link	c.86G>A	p.Arg29Gln	missense_variant	Exon 2 of 10	ENST00000216075.11	NP_060054.4	Q9UGB7-1
MIOX	XM_011530705.3 link	c.86G>A	p.Arg29Gln	missense_variant	Exon 2 of 6		XP_011529007.1
MIOX	XM_047441443.1 link	c.86G>A	p.Arg29Gln	missense_variant	Exon 2 of 9		XP_047297399.1
MIOX	XM_005261925.5 link	c.-49G>A		5_prime_UTR_variant	Exon 1 of 9		XP_005261982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MIOX	ENST00000216075.11 link	c.86G>A	p.Arg29Gln	missense_variant	Exon 2 of 10	1	NM_017584.6	ENSP00000216075.6	Q9UGB7-1
MIOX	ENST00000395732.7 link	c.86G>A	p.Arg29Gln	missense_variant	Exon 2 of 10	1		ENSP00000379081.3	A6PVH2
MIOX	ENST00000395733.7 link	c.86G>A	p.Arg29Gln	missense_variant	Exon 2 of 8	1		ENSP00000379082.3	Q9UGB7-2
MIOX	ENST00000451761.1 link	c.71G>A	p.Arg24Gln	missense_variant	Exon 1 of 9	3		ENSP00000409894.1	A6PVH4

Frequencies

GnomAD3 genomes

AF:

0.000408

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00125

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000215

AC:

AN:

250770

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135620

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00162

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000122

AC:

178

AN:

1461442

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.00167

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000414

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000578

AC XY:

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000116

Hom.:

Bravo

AF:

0.000268

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000173

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 16, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.86G>A (p.R29Q) alteration is located in exon 2 (coding exon 2) of the MIOX gene. This alteration results from a G to A substitution at nucleotide position 86, causing the arginine (R) at amino acid position 29 to be replaced by a glutamine (Q). 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

0.87

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.62

.;D;.;.

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

D;D;D;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.044

T;T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.5

M;M;.;.

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.5

D;D;D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.014

D;D;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.43

MVP

0.30

MPC

0.37

ClinPred

0.13

GERP RS

3.6

Varity_R

0.54

gMVP

0.86

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.

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