chr6-7393228-T-A

Variant names:

• chr6-7393228-T-A
• NM_031480.3:c.201T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031480.3(RIOK1):​c.201T>A​(p.Asp67Glu) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RIOK1 NM_031480.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.89
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039965868).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031480.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIOK1	NM_031480.3	MANE Select	c.201T>A	p.Asp67Glu	missense	Exon 2 of 17	NP_113668.2
	RIOK1	NM_001348194.2		c.-144T>A		5_prime_UTR	Exon 2 of 17	NP_001335123.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIOK1	ENST00000379834.7	TSL:1 MANE Select	c.201T>A	p.Asp67Glu	missense	Exon 2 of 17	ENSP00000369162.2	Q9BRS2
	RIOK1	ENST00000475351.5	TSL:1	n.201T>A		non_coding_transcript_exon	Exon 2 of 8	ENSP00000418263.1	E9PFQ8
	RIOK1	ENST00000967571.1		c.201T>A	p.Asp67Glu	missense	Exon 2 of 18	ENSP00000637630.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.12
DANN	Benign	0.96
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.6	L
PhyloP100		-1.9
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.032
Sift	Benign	0.13	T
Sift4G	Benign	0.25	T
Polyphen		0.0070	B
Vest4		0.12
MutPred		0.29		Gain of relative solvent accessibility (P = 0.09)
MVP		0.17
MPC		0.17
ClinPred		0.093	T
GERP RS		0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.046
gMVP		0.029
Mutation Taster		=90/10	polymorphism

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

hg19: chr6-7393461;