Variant 5-97167887-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_018343.3(RIOK2):c.977T>C(p.Ile326Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,461,062 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 Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

RIOK2
NM_018343.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.369

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03665322).

BP6

Variant 5-97167887-A-G is Benign according to our data. Variant chr5-97167887-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3154469.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIOK2	NM_018343.3 linkuse as main transcript	c.977T>C	p.Ile326Thr	missense_variant	8/10	ENST00000283109.8	NP_060813.2	Q9BVS4-1
RIOK2	NM_001159749.2 linkuse as main transcript	c.977T>C	p.Ile326Thr	missense_variant	8/8		NP_001153221.1	Q9BVS4-2
RIOK2	XM_017009628.2 linkuse as main transcript	c.416T>C	p.Ile139Thr	missense_variant	6/8		XP_016865117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RIOK2	ENST00000283109.8 linkuse as main transcript	c.977T>C	p.Ile326Thr	missense_variant	8/10	1	NM_018343.3	ENSP00000283109.3	Q9BVS4-1
RIOK2	ENST00000508447.1 linkuse as main transcript	c.977T>C	p.Ile326Thr	missense_variant	8/8	1		ENSP00000420932.1	Q9BVS4-2
LIX1-AS1	ENST00000504578.2 linkuse as main transcript	n.574-15121A>G		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250472

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135476

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1461062

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726858

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.0030

DANN

Benign

0.62

DEOGEN2

Benign

0.0024

T;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.33

T;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.037

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

0.85

N;N

REVEL

Benign

0.0080

Sift

Benign

0.70

T;T

Sift4G

Benign

0.57

T;T

Polyphen

0.0

B;.

Vest4

0.020

MutPred

0.23

Gain of phosphorylation at I326 (P = 0.0071);Gain of phosphorylation at I326 (P = 0.0071);

MVP

0.26

MPC

0.18

ClinPred

0.030

GERP RS

-8.4

Varity_R

0.012

gMVP

0.071

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

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