Variant 5-97167651-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018343.3(RIOK2):c.1213G>C(p.Gly405Arg) 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 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

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: 1.58

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08206484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RIOK2	NM_018343.3 linkuse as main transcript	c.1213G>C	p.Gly405Arg	missense_variant	8/10	ENST00000283109.8	NP_060813.2
RIOK2	NM_001159749.2 linkuse as main transcript	c.1213G>C	p.Gly405Arg	missense_variant	8/8		NP_001153221.1
RIOK2	XM_017009628.2 linkuse as main transcript	c.652G>C	p.Gly218Arg	missense_variant	6/8		XP_016865117.1
LIX1-AS1	XR_007058883.1 linkuse as main transcript	n.4605-15357C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIOK2	ENST00000283109.8 linkuse as main transcript	c.1213G>C	p.Gly405Arg	missense_variant	8/10	1	NM_018343.3	ENSP00000283109	P1	Q9BVS4-1
RIOK2	ENST00000508447.1 linkuse as main transcript	c.1213G>C	p.Gly405Arg	missense_variant	8/8	1		ENSP00000420932		Q9BVS4-2
LIX1-AS1	ENST00000504578.2 linkuse as main transcript	n.574-15357C>G		intron_variant, non_coding_transcript_variant		5
RIOK2	ENST00000511012.1 linkuse as main transcript	c.70G>C	p.Gly24Arg	missense_variant	1/2	2		ENSP00000422772

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461832

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 17, 2024

The c.1213G>C (p.G405R) alteration is located in exon 8 (coding exon 8) of the RIOK2 gene. This alteration results from a G to C substitution at nucleotide position 1213, causing the glycine (G) at amino acid position 405 to be replaced by an arginine (R). 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

0.081

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.0082

T;.

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.082

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.69

N;N

REVEL

Benign

0.054

Sift

Benign

0.32

T;T

Sift4G

Benign

0.28

T;T

Polyphen

0.014

B;.

Vest4

0.058

MutPred

0.21

Gain of methylation at K404 (P = 0.0368);Gain of methylation at K404 (P = 0.0368);

MVP

0.51

MPC

0.17

ClinPred

0.18

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.051

gMVP

0.37

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over