5-97167651-C-T

Variant names:

• chr5-97167651-C-T
• rs1748884534
• NM_018343.3:c.1213G>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.1213G>A​(p.Gly405Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RIOK2 NM_018343.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58
• 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=0.057397872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIOK2	NM_018343.3	c.1213G>A	p.Gly405Arg	missense_variant	Exon 8 of 10	ENST00000283109.8	NP_060813.2
RIOK2	NM_001159749.2	c.1213G>A	p.Gly405Arg	missense_variant	Exon 8 of 8		NP_001153221.1
RIOK2	XM_017009628.2	c.652G>A	p.Gly218Arg	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.1213G>A	p.Gly405Arg	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	0.081
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Benign	0.83
DEOGEN2	Benign	0.0082	T;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.057	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	2.0	M;M
PhyloP100		1.6
PrimateAI	Benign	0.24	T
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		0.40
MPC		0.17
ClinPred		0.18	T
GERP RS		3.3
PromoterAI		0.0038	Neutral
Varity_R		0.051
gMVP		0.37
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1748884534; hg19: chr5-96503355;