Variant 6-7390052-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_031480.3(RIOK1):c.50A>C(p.Asp17Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000071 in 1,407,680 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

RIOK1
NM_031480.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.39

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	UniProt
RIOK1	NM_031480.3 link	c.50A>C	p.Asp17Ala	missense_variant	1/17	ENST00000379834.7	NP_113668.2
RIOK1	NM_001348194.2 link	c.-295A>C		5_prime_UTR_variant	1/17		NP_001335123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIOK1	ENST00000379834.7 link	c.50A>C	p.Asp17Ala	missense_variant	1/17	1	NM_031480.3	ENSP00000369162.2		Q9BRS2
RIOK1	ENST00000475351.5 link	n.50A>C		non_coding_transcript_exon_variant	1/8	1		ENSP00000418263.1		E9PFQ8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000603

AC:

AN:

165798

Hom.:

AF XY:

0.00

AC XY:

AN XY:

89026

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:

0.0000152

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.10e-7

AC:

AN:

1407680

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

695338

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:

9.23e-7

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 27, 2024

The c.50A>C (p.D17A) alteration is located in exon 1 (coding exon 1) of the RIOK1 gene. This alteration results from a A to C substitution at nucleotide position 50, causing the aspartic acid (D) at amino acid position 17 to be replaced by an alanine (A). 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

0.41

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.050

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.80

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.15

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.013

Polyphen

0.92

Vest4

0.69

MutPred

0.52

Loss of disorder (P = 0.0846);

MVP

0.22

MPC

0.80

ClinPred

0.98

GERP RS

3.5

Varity_R

0.70

gMVP

0.22

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