Variant 5-97168817-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018343.3(RIOK2):c.815T>G(p.Phe272Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,450,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RIOK2
NM_018343.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.77

Variant links:

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]

RIOK2 links:

LIX1-AS1 (HGNC:):

LIX1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.938

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIOK2	NM_018343.3 linkuse as main transcript	c.815T>G	p.Phe272Cys	missense_variant	7/10	ENST00000283109.8	NP_060813.2	Q9BVS4-1
RIOK2	NM_001159749.2 linkuse as main transcript	c.815T>G	p.Phe272Cys	missense_variant	7/8		NP_001153221.1	Q9BVS4-2
RIOK2	XM_017009628.2 linkuse as main transcript	c.254T>G	p.Phe85Cys	missense_variant	5/8		XP_016865117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RIOK2	ENST00000283109.8 linkuse as main transcript	c.815T>G	p.Phe272Cys	missense_variant	7/10	1	NM_018343.3	ENSP00000283109.3	Q9BVS4-1
RIOK2	ENST00000508447.1 linkuse as main transcript	c.815T>G	p.Phe272Cys	missense_variant	7/8	1		ENSP00000420932.1	Q9BVS4-2
LIX1-AS1	ENST00000504578.2 linkuse as main transcript	n.574-14191A>C		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000414

AC:

AN:

241650

Hom.:

AF XY:

0.00

AC XY:

AN XY:

130680

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000315

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1450712

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721582

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000240

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2024

The c.815T>G (p.F272C) alteration is located in exon 7 (coding exon 7) of the RIOK2 gene. This alteration results from a T to G substitution at nucleotide position 815, causing the phenylalanine (F) at amino acid position 272 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Uncertain

0.045

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.18

T;.

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.047

MetaRNN

Pathogenic

0.94

D;D

MetaSVM

Benign

-0.64

MutationAssessor

Pathogenic

3.7

H;H

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-7.3

D;D

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.014

D;D

Polyphen

1.0

D;.

Vest4

0.97

MutPred

0.79

Gain of loop (P = 0.0435);Gain of loop (P = 0.0435);

MVP

0.79

MPC

0.74

ClinPred

1.0

GERP RS

5.8

Varity_R

0.96

gMVP

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over