chr5-97163200-C-T

Position:

• chr5-97163200-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_018343.3(RIOK2):​c.1520G>A​(p.Arg507His) variant causes a missense change. The variant allele was found at a frequency of 0.00247 in 1,613,396 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.012 (38 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (36 hom.)
• Consequence: RIOK2 NM_018343.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.80

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]

LIX1-AS1 (HGNC:52976): (LIX1 and RIOK2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0051208735).
• BP6: Variant 5-97163200-C-T is Benign according to our data. Variant chr5-97163200-C-T is described in ClinVar as [Benign]. Clinvar id is 768022.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0125 (1896/152250) while in subpopulation AFR AF= 0.0422 (1754/41544). AF 95% confidence interval is 0.0406. There are 38 homozygotes in gnomad4. There are 927 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIOK2	NM_018343.3	c.1520G>A	p.Arg507His	missense_variant	10/10	ENST00000283109.8	NP_060813.2
RIOK2	XM_017009628.2	c.959G>A	p.Arg320His	missense_variant	8/8		XP_016865117.1
LIX1-AS1	XR_007058883.1	n.4605-19808C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIOK2	ENST00000283109.8	c.1520G>A	p.Arg507His	missense_variant	10/10	1	NM_018343.3	ENSP00000283109	P1
LIX1-AS1	ENST00000504578.2	n.574-19808C>T		intron_variant, non_coding_transcript_variant		5
RIOK2	ENST00000511293.1	c.341G>A	p.Arg114His	missense_variant	4/4	3		ENSP00000421830

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1886 AN: 152132 Hom.: 38 Cov.: 32

Gnomad AFR AF: 0.0421

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00622

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.00909

GnomAD3 exomes AF: 0.00331 AC: 822 AN: 248654 Hom.: 13 AF XY: 0.00237 AC XY: 319 AN XY: 134616

Gnomad AFR exome AF: 0.0438

Gnomad AMR exome AF: 0.00206

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000655

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000216

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00143 AC: 2093 AN: 1461146 Hom.: 36 Cov.: 32 AF XY: 0.00125 AC XY: 905 AN XY: 726888

Gnomad4 AFR exome AF: 0.0461

Gnomad4 AMR exome AF: 0.00260

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.0000376

Gnomad4 NFE exome AF: 0.000188

Gnomad4 OTH exome AF: 0.00318

GnomAD4 genome AF: 0.0125 AC: 1896 AN: 152250 Hom.: 38 Cov.: 32 AF XY: 0.0125 AC XY: 927 AN XY: 74434

Gnomad4 AFR AF: 0.0422

Gnomad4 AMR AF: 0.00621

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.00326 Hom.: 20

Bravo AF: 0.0152

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0422 AC: 186

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00390 AC: 473

Asia WGS AF: 0.00115 AC: 4 AN: 3476

EpiCase AF: 0.000600

EpiControl AF: 0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.41
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.0051	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.15
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.056	T
Polyphen		1.0	D
Vest4		0.44
MVP		0.66
MPC		0.67
ClinPred		0.035	T
GERP RS		4.8
Varity_R		0.48
gMVP		0.21

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

Other links and lift over

dbSNP: rs34555783; hg19: chr5-96498904;