NM_018343.3:c.780-235T>C

Variant names:

• chr5-97169087-A-G
• rs10515254
• NM_018343.3:c.780-235T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018343.3(RIOK2):​c.780-235T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0804 in 152,274 control chromosomes in the GnomAD database, including 866 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.080 (866 hom., cov: 32)
• Consequence: RIOK2 NM_018343.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIOK2	NM_018343.3	c.780-235T>C		intron_variant	Intron 6 of 9	ENST00000283109.8	NP_060813.2
RIOK2	NM_001159749.2	c.780-235T>C		intron_variant	Intron 6 of 7		NP_001153221.1
RIOK2	XM_017009628.2	c.219-235T>C		intron_variant	Intron 4 of 7		XP_016865117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIOK2	ENST00000283109.8	c.780-235T>C		intron_variant	Intron 6 of 9	1	NM_018343.3	ENSP00000283109.3
RIOK2	ENST00000508447.1	c.780-235T>C		intron_variant	Intron 6 of 7	1		ENSP00000420932.1
LIX1-AS1	ENST00000504578.2	n.574-13921A>G		intron_variant	Intron 3 of 6	5

Frequencies

GnomAD3 genomes AF: 0.0804 AC: 12232 AN: 152156 Hom.: 869 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0535

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0391

Gnomad FIN AF: 0.0450

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.0802

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0804 AC: 12250 AN: 152274 Hom.: 866 Cov.: 32 AF XY: 0.0795 AC XY: 5921 AN XY: 74448

African (AFR) AF: 0.187 AC: 7773 AN: 41526

American (AMR) AF: 0.0535 AC: 818 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 586 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.0391 AC: 189 AN: 4830

European-Finnish (FIN) AF: 0.0450 AC: 478 AN: 10616

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.0319 AC: 2169 AN: 68014

Other (OTH) AF: 0.0794 AC: 168 AN: 2116

Alfa AF: 0.0646 Hom.: 86

Bravo AF: 0.0838

Asia WGS AF: 0.0290 AC: 103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.6
DANN	Benign	0.76
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10515254; hg19: chr5-96504791;