5-97163200-C-A

Variant names:

• chr5-97163200-C-A
• rs34555783
• NM_018343.3:c.1520G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018343.3(RIOK2):​c.1520G>T​(p.Arg507Leu) 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. R507H) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RIOK2 NM_018343.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.80

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23149192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIOK2	NM_018343.3	c.1520G>T	p.Arg507Leu	missense_variant	Exon 10 of 10	ENST00000283109.8	NP_060813.2
RIOK2	XM_017009628.2	c.959G>T	p.Arg320Leu	missense_variant	Exon 8 of 8		XP_016865117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIOK2	ENST00000283109.8	c.1520G>T	p.Arg507Leu	missense_variant	Exon 10 of 10	1	NM_018343.3	ENSP00000283109.3
RIOK2	ENST00000511293.1	c.338G>T	p.Arg113Leu	missense_variant	Exon 4 of 4	3		ENSP00000421830.1
LIX1-AS1	ENST00000504578.2	n.574-19808C>A		intron_variant	Intron 3 of 6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248654 Hom.: 0 AF XY: 0.00000743 AC XY: 1 AN XY: 134616

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000898

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.0069
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.17
Sift	Benign	0.12	T
Sift4G	Benign	0.29	T
Polyphen		0.30	B
Vest4		0.51
MutPred		0.24		Loss of loop (P = 0.0128);
MVP		0.48
MPC		0.26
ClinPred		0.86	D
GERP RS		4.8
Varity_R		0.58
gMVP		0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs34555783; hg19: chr5-96498904;