Variant 22-50489527-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_017584.6(MIOX):c.637-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00626 in 1,612,532 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 47 hom. )

Consequence

MIOX
NM_017584.6 splice_region, intron

Scores

Splicing: ADA: 0.0002052

Clinical Significance

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

Conservation

PhyloP100: 0.0510

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 22-50489527-C-T is Benign according to our data. Variant chr22-50489527-C-T is described in ClinVar as [Benign]. Clinvar id is 710094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MIOX	NM_017584.6 linkuse as main transcript	c.637-5C>T	splice_region_variant, intron_variant	ENST00000216075.11	NP_060054.4	Q9UGB7-1
MIOX	XM_005261925.5 linkuse as main transcript	c.499-5C>T	splice_region_variant, intron_variant		XP_005261982.1
MIOX	XM_047441443.1 linkuse as main transcript	c.*33-5C>T	splice_region_variant, intron_variant		XP_047297399.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MIOX	ENST00000216075.11 linkuse as main transcript	c.637-5C>T	splice_region_variant, intron_variant	1	NM_017584.6	ENSP00000216075.6	Q9UGB7-1
MIOX	ENST00000395732.7 linkuse as main transcript	c.637-5C>T	splice_region_variant, intron_variant	1		ENSP00000379081.3	A6PVH2
MIOX	ENST00000395733.7 linkuse as main transcript	c.619-221C>T	intron_variant	1		ENSP00000379082.3	Q9UGB7-2
MIOX	ENST00000451761.1 linkuse as main transcript	c.577-5C>T	splice_region_variant, intron_variant	3		ENSP00000409894.1	A6PVH4

Frequencies

GnomAD3 genomes

AF:

0.00561

AC:

853

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00835

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.0113

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00890

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00630

AC:

1565

AN:

248422

Hom.:

AF XY:

0.00612

AC XY:

827

AN XY:

135158

show subpopulations

Gnomad AFR exome

AF:

0.00100

Gnomad AMR exome

AF:

0.00267

Gnomad ASJ exome

AF:

0.00999

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.00288

Gnomad FIN exome

AF:

0.0135

Gnomad NFE exome

AF:

0.00820

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.00633

AC:

9241

AN:

1460276

Hom.:

Cov.:

AF XY:

0.00633

AC XY:

4597

AN XY:

726462

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00289

Gnomad4 ASJ exome

AF:

0.00974

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00307

Gnomad4 FIN exome

AF:

0.0134

Gnomad4 NFE exome

AF:

0.00672

Gnomad4 OTH exome

AF:

0.00583

GnomAD4 genome

AF:

0.00560

AC:

852

AN:

152256

Hom.:

Cov.:

AF XY:

0.00563

AC XY:

419

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00835

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.0113

Gnomad4 NFE

AF:

0.00890

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00804

Hom.:

Bravo

AF:

0.00441

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00818

EpiControl

AF:

0.00794

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 02, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.0

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00021

dbscSNV1_RF

Benign

0.078

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