NM_018343.3:c.1261A>C

Variant names:

• chr5-97167603-T-G
• rs1748882714
• NM_018343.3:c.1261A>C

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.1261A>C​(p.Asn421His) 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. 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: 0.955
• 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: 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=0.08117688).

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.1261A>C	p.Asn421His	missense	Exon 8 of 10	NP_060813.2	Q9BVS4-1
	RIOK2	NM_001159749.2		c.1261A>C	p.Asn421His	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.1261A>C	p.Asn421His	missense	Exon 8 of 10	ENSP00000283109.3	Q9BVS4-1
	RIOK2	ENST00000508447.1	TSL:1	c.1261A>C	p.Asn421His	missense	Exon 8 of 8	ENSP00000420932.1	Q9BVS4-2
	RIOK2	ENST00000924329.1		c.1258A>C	p.Asn420His	missense	Exon 8 of 10	ENSP00000594388.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.072
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	11
DANN	Benign	0.96
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.95
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.043
Sift	Benign	0.055	T
Sift4G	Benign	0.13	T
Polyphen		0.53	P
Vest4		0.14
MutPred		0.12		Loss of methylation at K420 (P = 0.1415)
MVP		0.45
MPC		0.21
ClinPred		0.14	T
GERP RS		0.20
PromoterAI		0.053	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.045
gMVP		0.087
Mutation Taster		=93/7	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: rs1748882714; hg19: chr5-96503307;