5-97167749-T-C

Variant names:

• chr5-97167749-T-C
• rs1580267359
• NM_018343.3:c.1115A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018343.3(RIOK2):​c.1115A>G​(p.Asp372Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RIOK2 NM_018343.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.43

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 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=0.09619284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIOK2	NM_018343.3	c.1115A>G	p.Asp372Gly	missense_variant	Exon 8 of 10	ENST00000283109.8	NP_060813.2
RIOK2	NM_001159749.2	c.1115A>G	p.Asp372Gly	missense_variant	Exon 8 of 8		NP_001153221.1
RIOK2	XM_017009628.2	c.554A>G	p.Asp185Gly	missense_variant	Exon 6 of 8		XP_016865117.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIOK2	ENST00000283109.8	c.1115A>G	p.Asp372Gly	missense_variant	Exon 8 of 10	1	NM_018343.3	ENSP00000283109.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 16, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1115A>G (p.D372G) alteration is located in exon 8 (coding exon 8) of the RIOK2 gene. This alteration results from a A to G substitution at nucleotide position 1115, causing the aspartic acid (D) at amino acid position 372 to be replaced by a glycine (G). 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	0.074
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.0065	T;.
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.096	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.075
Sift	Benign	0.056	T;D
Sift4G	Benign	0.24	T;T
Polyphen		0.062	B;.
Vest4		0.15
MutPred		0.16		Gain of catalytic residue at D372 (P = 0.0693);Gain of catalytic residue at D372 (P = 0.0693);
MVP		0.26
MPC		0.19
ClinPred		0.082	T
GERP RS		2.1
Varity_R		0.058
gMVP		0.17

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: rs1580267359; hg19: chr5-96503453;