5-97167726-T-G

Variant names:

• chr5-97167726-T-G
• rs191630960
• NM_018343.3:c.1138A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PM1 PM2 BP4_Strong

The NM_018343.3(RIOK2):​c.1138A>C​(p.Ser380Arg) 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. 15/22 in silico tools predict 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. S380G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RIOK2 NM_018343.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.903
• 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.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity RIOK2_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052191764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIOK2	NM_018343.3	c.1138A>C	p.Ser380Arg	missense_variant	Exon 8 of 10	ENST00000283109.8	NP_060813.2
RIOK2	NM_001159749.2	c.1138A>C	p.Ser380Arg	missense_variant	Exon 8 of 8		NP_001153221.1
RIOK2	XM_017009628.2	c.577A>C	p.Ser193Arg	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.1138A>C	p.Ser380Arg	missense_variant	Exon 8 of 10	1	NM_018343.3	ENSP00000283109.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.023
DANN	Benign	0.62
DEOGEN2	Benign	0.0050	T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.49	T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.052	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M
PhyloP100		-0.90
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.95	N;N
REVEL	Benign	0.096
Sift	Benign	0.40	T;T
Sift4G	Benign	0.34	T;T
Polyphen		0.018	B;.
Vest4		0.20
MutPred		0.13		Loss of phosphorylation at S380 (P = 0.0028);Loss of phosphorylation at S380 (P = 0.0028);
MVP		0.13
MPC		0.16
ClinPred		0.053	T
GERP RS		-10
PromoterAI		-0.00080	Neutral
Varity_R		0.047
gMVP		0.10
Mutation Taster		=85/15	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: rs191630960; hg19: chr5-96503430;