Variant 6-7393243-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000379834.7(RIOK1):c.216G>C(p.Trp72Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,790 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RIOK1
ENST00000379834.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.56

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RIOK1	NM_031480.3 linkuse as main transcript	c.216G>C	p.Trp72Cys	missense_variant	2/17	ENST00000379834.7	NP_113668.2
RIOK1	XM_011514933.4 linkuse as main transcript	c.252G>C	p.Trp84Cys	missense_variant	2/17		XP_011513235.2
RIOK1	NM_001348194.2 linkuse as main transcript	c.-129G>C		5_prime_UTR_variant	2/17		NP_001335123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIOK1	ENST00000379834.7 linkuse as main transcript	c.216G>C	p.Trp72Cys	missense_variant	2/17	1	NM_031480.3	ENSP00000369162	P1
RIOK1	ENST00000475351.5 linkuse as main transcript	c.216G>C	p.Trp72Cys	missense_variant, NMD_transcript_variant	2/8	1		ENSP00000418263

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

249024

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134800

show subpopulations

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

AF:

0.00000137

AC:

AN:

1461790

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727198

show subpopulations

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 12, 2021

The c.216G>C (p.W72C) alteration is located in exon 2 (coding exon 2) of the RIOK1 gene. This alteration results from a G to C substitution at nucleotide position 216, causing the tryptophan (W) at amino acid position 72 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

Uncertain

0.54

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.80

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.3

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.15

Sift

Benign

0.035

Sift4G

Benign

0.18

Polyphen

1.0

Vest4

0.60

MutPred

0.48

Loss of helix (P = 0.0558);

MVP

0.64

MPC

0.86

ClinPred

0.99

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.54

gMVP

0.20

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