chr5-97167887-A-C

Variant names:

• chr5-97167887-A-C
• rs759975930
• NM_018343.3:c.977T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018343.3(RIOK2):​c.977T>G​(p.Ile326Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I326T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RIOK2 NM_018343.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046367377).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIOK2	NM_018343.3	c.977T>G	p.Ile326Ser	missense_variant	Exon 8 of 10	ENST00000283109.8	NP_060813.2
RIOK2	NM_001159749.2	c.977T>G	p.Ile326Ser	missense_variant	Exon 8 of 8		NP_001153221.1
RIOK2	XM_017009628.2	c.416T>G	p.Ile139Ser	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.977T>G	p.Ile326Ser	missense_variant	Exon 8 of 10	1	NM_018343.3	ENSP00000283109.3
RIOK2	ENST00000508447.1	c.977T>G	p.Ile326Ser	missense_variant	Exon 8 of 8	1		ENSP00000420932.1
LIX1-AS1	ENST00000504578.2	n.574-15121A>C		intron_variant	Intron 3 of 6	5
RIOK2	ENST00000511012.1	c.-170T>G		upstream_gene_variant		2		ENSP00000422772.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461062 Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3 AN XY: 726858

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.0050
DANN	Benign	0.67
DEOGEN2	Benign	0.0023	T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.28	T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.046	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.85	N;N
REVEL	Benign	0.0090
Sift	Benign	0.73	T;T
Sift4G	Benign	0.62	T;T
Polyphen		0.0	B;.
Vest4		0.052
MutPred		0.27		Gain of phosphorylation at I326 (P = 0.0148);Gain of phosphorylation at I326 (P = 0.0148);
MVP		0.28
MPC		0.21
ClinPred		0.029	T
GERP RS		-8.4
Varity_R		0.016
gMVP		0.12

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: rs759975930; hg19: chr5-96503591;