NM_018343.3:c.886C>G

Variant names:

• chr5-97167978-G-C
• rs755919408
• NM_018343.3:c.886C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018343.3(RIOK2):​c.886C>G​(p.Leu296Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000166 in 1,444,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: RIOK2 NM_018343.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.76
• Publications: 0 publications found

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]

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.17897484).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018343.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIOK2	NM_018343.3	MANE Select	c.886C>G	p.Leu296Val	missense	Exon 8 of 10	NP_060813.2	Q9BVS4-1
	RIOK2	NM_001159749.2		c.886C>G	p.Leu296Val	missense	Exon 8 of 8	NP_001153221.1	Q9BVS4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIOK2	ENST00000283109.8	TSL:1 MANE Select	c.886C>G	p.Leu296Val	missense	Exon 8 of 10	ENSP00000283109.3	Q9BVS4-1
	RIOK2	ENST00000508447.1	TSL:1	c.886C>G	p.Leu296Val	missense	Exon 8 of 8	ENSP00000420932.1	Q9BVS4-2
	RIOK2	ENST00000924329.1		c.883C>G	p.Leu295Val	missense	Exon 8 of 10	ENSP00000594388.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000974 AC: 23 AN: 236120 AF XY: 0.0000465

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000692

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000166 AC: 24 AN: 1444218 Hom.: 0 Cov.: 34 AF XY: 0.0000139 AC XY: 10 AN XY: 718636

African (AFR) AF: 0.00 AC: 0 AN: 32962

American (AMR) AF: 0.000530 AC: 23 AN: 43358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25730

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.00 AC: 0 AN: 85484

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1109038

Other (OTH) AF: 0.00 AC: 0 AN: 60018

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000604

ExAC AF: 0.0000660 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		5.8
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.16
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.43
MutPred		0.33		Loss of sheet (P = 0.0084)
MVP		0.72
MPC		0.26
ClinPred		0.30	T
GERP RS		4.8
PromoterAI		0.031	Neutral
Varity_R		0.26
gMVP		0.48
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs755919408; hg19: chr5-96503682;