Variant 22-50489426-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017584.6(MIOX):c.616A>G(p.Lys206Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000642 in 1,603,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

MIOX
NM_017584.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.06

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034747124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIOX	NM_017584.6 linkuse as main transcript	c.616A>G	p.Lys206Glu	missense_variant	8/10	ENST00000216075.11	NP_060054.4	Q9UGB7-1
MIOX	XM_005261925.5 linkuse as main transcript	c.478A>G	p.Lys160Glu	missense_variant	7/9		XP_005261982.1
MIOX	XM_047441443.1 linkuse as main transcript	c.*12A>G		3_prime_UTR_variant	8/9		XP_047297399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MIOX	ENST00000216075.11 linkuse as main transcript	c.616A>G	p.Lys206Glu	missense_variant	8/10	1	NM_017584.6	ENSP00000216075.6	Q9UGB7-1
MIOX	ENST00000395732.7 linkuse as main transcript	c.616A>G	p.Lys206Glu	missense_variant	8/10	1		ENSP00000379081.3	A6PVH2
MIOX	ENST00000395733.7 linkuse as main transcript	c.618+131A>G		intron_variant		1		ENSP00000379082.3	Q9UGB7-2
MIOX	ENST00000451761.1 linkuse as main transcript	c.556A>G	p.Lys186Glu	missense_variant	7/9	3		ENSP00000409894.1	A6PVH4

Frequencies

GnomAD3 genomes

AF:

0.000382

AC:

AN:

151860

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

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:

0.000478

GnomAD3 exomes

AF:

0.0000741

AC:

AN:

243006

Hom.:

AF XY:

0.0000603

AC XY:

AN XY:

132688

show subpopulations

Gnomad AFR exome

AF:

0.00103

Gnomad AMR exome

AF:

0.0000292

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:

0.00000908

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000310

AC:

AN:

1451480

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

721394

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.0000450

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000100

GnomAD4 genome

AF:

0.000382

AC:

AN:

151860

Hom.:

Cov.:

AF XY:

0.000310

AC XY:

AN XY:

74150

show subpopulations

Gnomad4 AFR

AF:

0.00126

Gnomad4 AMR

AF:

0.000328

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000679

Hom.:

Bravo

AF:

0.000446

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000991

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 04, 2024

The c.616A>G (p.K206E) alteration is located in exon 8 (coding exon 8) of the MIOX gene. This alteration results from a A to G substitution at nucleotide position 616, causing the lysine (K) at amino acid position 206 to be replaced by a glutamic acid (E). 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

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.089

T;.;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.76

T;T;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.035

T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.3

M;.;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.063

Sift

Benign

0.12

T;T;T

Sift4G

Benign

0.35

T;T;T

Polyphen

0.0020

B;B;.

Vest4

0.24

MVP

0.19

MPC

0.073

ClinPred

0.030

GERP RS

4.1

Varity_R

0.36

gMVP

0.61

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.

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