Variant 3-97945822-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_153182.4(RIOX2):c.1215G>T(p.Met405Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000233 in 1,610,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

RIOX2
NM_153182.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.64

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.803

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIOX2	NM_153182.4 link	c.1215G>T	p.Met405Ile	missense_variant	9/10	ENST00000394198.7	NP_694822.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIOX2	ENST00000394198.7 link	c.1215G>T	p.Met405Ile	missense_variant	9/10	1	NM_153182.4	ENSP00000377748.2		Q8IUF8-1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000759

AC:

AN:

250458

Hom.:

AF XY:

0.0000960

AC XY:

AN XY:

135390

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000243

AC:

354

AN:

1458568

Hom.:

Cov.:

AF XY:

0.000278

AC XY:

202

AN XY:

725712

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000673

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000306

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000138

AC:

AN:

152092

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000179

Hom.:

Bravo

AF:

0.000121

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

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

Dec 13, 2022

The c.1215G>T (p.M405I) alteration is located in exon 9 (coding exon 8) of the MINA gene. This alteration results from a G to T substitution at nucleotide position 1215, causing the methionine (M) at amino acid position 405 to be replaced by an isoleucine (I). 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

Pathogenic

0.98

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;T;.

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

.;D;D

M_CAP

Benign

0.027

MetaRNN

Pathogenic

0.80

D;D;D

MetaSVM

Benign

-0.96

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.5

D;D;D

REVEL

Benign

0.28

Sift

Pathogenic

0.0

D;D;D

Sift4G

Uncertain

0.015

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.77

MutPred

0.36

Loss of disorder (P = 0.144);Loss of disorder (P = 0.144);.;

MVP

0.65

MPC

0.42

ClinPred

0.95

GERP RS

6.1

Varity_R

0.89

gMVP

0.54

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

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