5-97167473-G-T

Variant names:

• chr5-97167473-G-T
• rs143694844
• NM_018343.3:c.1391C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018343.3(RIOK2):​c.1391C>A​(p.Pro464His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P464L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RIOK2 NM_018343.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.62
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22756764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIOK2	NM_018343.3	c.1391C>A	p.Pro464His	missense_variant	Exon 8 of 10	ENST00000283109.8	NP_060813.2
RIOK2	NM_001159749.2	c.1391C>A	p.Pro464His	missense_variant	Exon 8 of 8		NP_001153221.1
RIOK2	XM_017009628.2	c.830C>A	p.Pro277His	missense_variant	Exon 6 of 8		XP_016865117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIOK2	ENST00000283109.8	c.1391C>A	p.Pro464His	missense_variant	Exon 8 of 10	1	NM_018343.3	ENSP00000283109.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T;.
Eigen	Benign	0.14
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.3	M;M
PhyloP100		5.6
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-4.3	D;D
REVEL	Benign	0.14
Sift	Benign	0.16	T;D
Sift4G	Benign	0.13	T;D
Polyphen		0.010	B;.
Vest4		0.082
MutPred		0.46		Loss of stability (P = 0.0829);Loss of stability (P = 0.0829);
MVP		0.72
MPC		0.17
ClinPred		0.94	D
GERP RS		4.9
PromoterAI		-0.029	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.32
Mutation Taster		=67/33	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

dbSNP: rs143694844; hg19: chr5-96503177;