chr5-97167645-C-T

Variant names:

• chr5-97167645-C-T
• NM_018343.3:c.1219G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018343.3(RIOK2):​c.1219G>A​(p.Val407Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: RIOK2 NM_018343.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.815
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041713983).

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.1219G>A	p.Val407Ile	missense	Exon 8 of 10	NP_060813.2	Q9BVS4-1
	RIOK2	NM_001159749.2		c.1219G>A	p.Val407Ile	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.1219G>A	p.Val407Ile	missense	Exon 8 of 10	ENSP00000283109.3	Q9BVS4-1
	RIOK2	ENST00000508447.1	TSL:1	c.1219G>A	p.Val407Ile	missense	Exon 8 of 8	ENSP00000420932.1	Q9BVS4-2
	RIOK2	ENST00000924329.1		c.1216G>A	p.Val406Ile	missense	Exon 8 of 10	ENSP00000594388.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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	0.063
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.4
DANN	Benign	0.70
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.95	L
PhyloP100		-0.81
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.016
Sift	Benign	0.49	T
Sift4G	Benign	0.28	T
Polyphen		0.0	B
Vest4		0.018
MutPred		0.15		Gain of methylation at K404 (P = 0.1116)
MVP		0.29
MPC		0.11
ClinPred		0.025	T
GERP RS		0.72
PromoterAI		0.043	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.012
gMVP		0.054
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

hg19: chr5-96503349;