Genetic Variant NM_017584.6:c.329A>G (chr22-50488037-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_017584.6(MIOX):c.329A>G(p.His110Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000599 in 1,613,488 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00054 ( 8 hom. )

Consequence

MIOX
NM_017584.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.17

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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010762155).

BP6

Variant 22-50488037-A-G is Benign according to our data. Variant chr22-50488037-A-G is described in ClinVar as Benign. ClinVar VariationId is 771546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.000542 (792/1461296) while in subpopulation AMR AF = 0.0167 (745/44706). AF 95% confidence interval is 0.0157. There are 8 homozygotes in GnomAdExome4. There are 332 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

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.329A>G	p.His110Arg	missense	Exon 4 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.329A>G	p.His110Arg	missense	Exon 4 of 10	ENSP00000216075.6	Q9UGB7-1
MIOX	ENST00000395732.7	TSL:1	c.329A>G	p.His110Arg	missense	Exon 4 of 10	ENSP00000379081.3	A6PVH2
MIOX	ENST00000395733.7	TSL:1	c.329A>G	p.His110Arg	missense	Exon 4 of 8	ENSP00000379082.3	Q9UGB7-2

Frequencies

GnomAD3 genomes

AF:

0.00115

AC:

175

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0102

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:

0.0000588

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00243

AC:

607

AN:

250066

AF XY:

0.00186

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000542

AC:

792

AN:

1461296

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

332

AN XY:

726950

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

33478

American (AMR)

AF:

0.0167

AC:

745

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53080

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00000809

AC:

AN:

1111850

Other (OTH)

AF:

0.000480

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

104

155

207

259

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00115

AC:

175

AN:

152192

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

106

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41520

American (AMR)

AF:

0.0101

AC:

155

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67994

Other (OTH)

AF:

0.00284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000495

Hom.:

Bravo

AF:

0.00180

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00181

AC:

220

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.011

MetaSVM

Uncertain

-0.24

MutationAssessor

Uncertain

2.7

PhyloP100

4.2

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-7.2

REVEL

Uncertain

0.36

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.62

MVP

0.26

MPC

0.38

ClinPred

0.098

GERP RS

4.2

Varity_R

0.71

gMVP

0.85

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over