dbSNP rs1748889946: RIOK2:p.Val341Leu (chr5-97167843-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018343.3(RIOK2):c.1021G>T(p.Val341Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RIOK2
NM_018343.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.25

Publications

0 publications found

Variant links:

Genes affected

RIOK2 (HGNC:18999): (RIO kinase 2) Predicted to enable protein kinase activity. Involved in several processes, including positive regulation of rRNA processing; positive regulation of ribosomal small subunit export from nucleus; and regulation of mitotic metaphase/anaphase transition. Located in cytoplasm. Part of preribosome, small subunit precursor. [provided by Alliance of Genome Resources, Apr 2022]

RIOK2 links:

LIX1-AS1 (HGNC:52976): (LIX1 and RIOK2 antisense RNA 1)

LIX1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.041143596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIOK2	NM_018343.3 link	c.1021G>T	p.Val341Leu	missense_variant	Exon 8 of 10	ENST00000283109.8	NP_060813.2	Q9BVS4-1
RIOK2	NM_001159749.2 link	c.1021G>T	p.Val341Leu	missense_variant	Exon 8 of 8		NP_001153221.1	Q9BVS4-2
RIOK2	XM_017009628.2 link	c.460G>T	p.Val154Leu	missense_variant	Exon 6 of 8		XP_016865117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RIOK2	ENST00000283109.8 link	c.1021G>T	p.Val341Leu	missense_variant	Exon 8 of 10	1	NM_018343.3	ENSP00000283109.3	Q9BVS4-1
RIOK2	ENST00000508447.1 link	c.1021G>T	p.Val341Leu	missense_variant	Exon 8 of 8	1		ENSP00000420932.1	Q9BVS4-2
LIX1-AS1	ENST00000504578.2 link	n.574-15165C>A		intron_variant	Intron 3 of 6	5
RIOK2	ENST00000511012.1 link	c.-126G>T		upstream_gene_variant		2		ENSP00000422772.1	H0Y919

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461612

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727108

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53336

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111938

Other (OTH)

AF:

0.00

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 14, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1021G>T (p.V341L) alteration is located in exon 8 (coding exon 8) of the RIOK2 gene. This alteration results from a G to T substitution at nucleotide position 1021, causing the valine (V) at amino acid position 341 to be replaced by a leucine (L). 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

0.086

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.1

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.0050

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.55

T;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.041

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L

PhyloP100

-1.2

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.49

N;N

REVEL

Benign

0.015

Sift

Benign

0.33

T;T

Sift4G

Benign

0.30

T;T

Polyphen

0.0010

B;.

Vest4

0.047

MutPred

0.33

Gain of loop (P = 3e-04);Gain of loop (P = 3e-04);

MVP

0.36

MPC

0.14

ClinPred

0.085

GERP RS

-5.1

PromoterAI

0.0018

Neutral

(source)

Varity_R

0.021

gMVP

0.088

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs1748889946

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over