Variant 6-7395140-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031480.3(RIOK1):c.364T>A(p.Leu122Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000944 in 1,609,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000095 ( 0 hom. )

Consequence

RIOK1
NM_031480.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.68

Variant links:

Genes affected

RIOK1 (HGNC:18656): (RIO kinase 1) The protein encoded by this gene competes with pICln for inclusion in the protein arginine methyltransferase 5 complex. This complex targets substrates for dimethylation. The encoded protein is essential for the last steps in the maturation of 40S subunits. [provided by RefSeq, Jan 2017]

RIOK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.10765493).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RIOK1	NM_031480.3 linkuse as main transcript	c.364T>A	p.Leu122Ile	missense_variant	3/17	ENST00000379834.7	NP_113668.2
RIOK1	NM_001348194.2 linkuse as main transcript	c.52T>A	p.Leu18Ile	missense_variant	3/17		NP_001335123.1
RIOK1	XM_011514933.4 linkuse as main transcript	c.400T>A	p.Leu134Ile	missense_variant	3/17		XP_011513235.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RIOK1	ENST00000379834.7 linkuse as main transcript	c.364T>A	p.Leu122Ile	missense_variant	3/17	1	NM_031480.3	ENSP00000369162.2	Q9BRS2
RIOK1	ENST00000475351.5 linkuse as main transcript	n.*108T>A		non_coding_transcript_exon_variant	3/8	1		ENSP00000418263.1	E9PFQ8
RIOK1	ENST00000475351.5 linkuse as main transcript	n.*108T>A		3_prime_UTR_variant	3/8	1		ENSP00000418263.1	E9PFQ8

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000534

AC:

AN:

243624

Hom.:

AF XY:

0.0000379

AC XY:

AN XY:

131782

show subpopulations

Gnomad AFR exome

AF:

0.000129

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:

0.000101

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000954

AC:

139

AN:

1457358

Hom.:

Cov.:

AF XY:

0.0000924

AC XY:

AN XY:

724746

show subpopulations

Gnomad4 AFR exome

AF:

0.0000603

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:

0.000119

Gnomad4 OTH exome

AF:

0.0000831

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000248

Hom.:

Bravo

AF:

0.0000869

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

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

Feb 27, 2023

The c.364T>A (p.L122I) alteration is located in exon 3 (coding exon 3) of the RIOK1 gene. This alteration results from a T to A substitution at nucleotide position 364, causing the leucine (L) at amino acid position 122 to be replaced by an isoleucine (I). 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

Benign

0.18

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0090

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.014

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.5

PrimateAI

Uncertain

0.63

PROVEAN

Benign

0.18

REVEL

Benign

0.12

Sift

Benign

0.17

Sift4G

Benign

0.39

Polyphen

0.43

Vest4

0.35

MVP

0.23

MPC

0.63

ClinPred

0.15

GERP RS

3.6

Varity_R

0.092

gMVP

0.18

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