Variant 18-23466245-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003831.5(RIOK3):c.656G>A(p.Arg219His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000696 in 1,609,650 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

RIOK3
NM_003831.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.75

Variant links:

Genes affected

RIOK3 (HGNC:11451): (RIO kinase 3) This gene was first identified by the similarity of its product to the Aspergillus nidulans SUDD protein. This gene is now recognized as a member of the right open reading frame (RIO) kinase gene family. This gene encodes a serine/threonine kinase that localizes to the cytoplasm and plays a role in the processing of the pre-40 S ribosomal subunit. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2017]

RIOK3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIOK3	NM_003831.5 linkuse as main transcript	c.656G>A	p.Arg219His	missense_variant	6/13	ENST00000339486.8	NP_003822.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIOK3	ENST00000339486.8 linkuse as main transcript	c.656G>A	p.Arg219His	missense_variant	6/13	1	NM_003831.5	ENSP00000341874	P1	O14730-1

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151588

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000736

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000105

AC:

AN:

248684

Hom.:

AF XY:

0.0000968

AC XY:

AN XY:

134294

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000296

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000336

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000204

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000734

AC:

107

AN:

1458062

Hom.:

Cov.:

AF XY:

0.0000759

AC XY:

AN XY:

725100

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000676

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000838

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000330

AC:

AN:

151588

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

73956

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000901

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000115

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

Sep 20, 2023

The c.656G>A (p.R219H) alteration is located in exon 6 (coding exon 6) of the RIOK3 gene. This alteration results from a G to A substitution at nucleotide position 656, causing the arginine (R) at amino acid position 219 to be replaced by a histidine (H). 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

Uncertain

0.55

BayesDel_addAF

Uncertain

0.033

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

T;.;.

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.91

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Benign

0.048

MetaRNN

Uncertain

0.64

D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.0

M;.;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.9

D;.;.

REVEL

Uncertain

0.56

Sift

Uncertain

0.0020

D;.;.

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.58

MVP

0.75

MPC

1.2

ClinPred

0.75

GERP RS

5.9

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Varity_R

0.45

gMVP

0.41

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