Variant 3-97947443-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153182.4(RIOX2):c.1067A>G(p.Lys356Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

RIOX2
NM_153182.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.175

Variant links:

Genes affected

RIOX2 (HGNC:19441): (ribosomal oxygenase 2) MINA is a c-Myc (MYC; MIM 190080) target gene that may play a role in cell proliferation or regulation of cell growth. (Tsuneoka et al., 2002 [PubMed 12091391]; Zhang et al., 2005 [PubMed 15897898]).[supplied by OMIM, May 2008]

RIOX2 links:

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ACMG classification

Classification made for transcript

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=0.039899558).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIOX2	NM_153182.4 link	c.1067A>G	p.Lys356Arg	missense_variant	8/10	ENST00000394198.7	NP_694822.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIOX2	ENST00000394198.7 link	c.1067A>G	p.Lys356Arg	missense_variant	8/10	1	NM_153182.4	ENSP00000377748.2		Q8IUF8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250702

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135484

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460898

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726784

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2023

The c.1067A>G (p.K356R) alteration is located in exon 8 (coding exon 7) of the MINA gene. This alteration results from a A to G substitution at nucleotide position 1067, causing the lysine (K) at amino acid position 356 to be replaced by an arginine (R). 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

0.067

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.2

DANN

Uncertain

0.98

DEOGEN2

Benign

0.027

T;T;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.092

LIST_S2

Benign

0.36

.;T;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.040

T;T;T

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.036

Sift

Benign

0.41

T;T;T

Sift4G

Benign

0.51

T;T;T

Polyphen

0.0040

B;B;B

Vest4

0.11

MutPred

0.38

Loss of ubiquitination at K356 (P = 0.0074);Loss of ubiquitination at K356 (P = 0.0074);.;

MVP

0.20

MPC

0.061

ClinPred

0.017

GERP RS

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.076

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over