5-97167651-C-G

Position:

• chr5-97167651-C-G

Variant summary

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

The NM_018343.3(RIOK2):​c.1213G>C​(p.Gly405Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RIOK2 NM_018343.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58

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=0.08206484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIOK2	NM_018343.3	c.1213G>C	p.Gly405Arg	missense_variant	8/10	ENST00000283109.8
RIOK2	NM_001159749.2	c.1213G>C	p.Gly405Arg	missense_variant	8/8
RIOK2	XM_017009628.2	c.652G>C	p.Gly218Arg	missense_variant	6/8
LIX1-AS1	XR_007058883.1	n.4605-15357C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIOK2	ENST00000283109.8	c.1213G>C	p.Gly405Arg	missense_variant	8/10	1	NM_018343.3	P1
RIOK2	ENST00000508447.1	c.1213G>C	p.Gly405Arg	missense_variant	8/8	1
LIX1-AS1	ENST00000504578.2	n.574-15357C>G		intron_variant, non_coding_transcript_variant		5
RIOK2	ENST00000511012.1	c.70G>C	p.Gly24Arg	missense_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461832 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727220

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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	14
DANN	Benign	0.84
DEOGEN2	Benign	0.0082	T;.
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.082	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;M
MutationTaster	Benign	1.0	N;N
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		0.51
MPC		0.17
ClinPred		0.18	T
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.051
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-96503355;