NM_001252499.3:c.22C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_001252499.3(RHNO1):c.22C>T(p.Arg8Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000417 in 1,613,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

RHNO1
NM_001252499.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.510

Variant links:

Genes affected

RHNO1 (HGNC:28206): (RAD9-HUS1-RAD1 interacting nuclear orphan 1) Involved in cellular response to radiation; recombinational repair; and regulation of cell cycle process. Located in chromosome and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RHNO1 links:

TULP3 (HGNC:12425): (TUB like protein 3) This gene encodes a member of the tubby gene family of bipartite transcription factors. Members of this family have been identified in plants, vertebrates, and invertebrates, and they share a conserved N-terminal transcription activation region and a conserved C-terminal DNA and phosphatidylinositol-phosphate binding region. The encoded protein binds to phosphoinositides in the plasma membrane via its C-terminal region and probably functions as a membrane-bound transcription regulator that translocates to the nucleus in response to phosphoinositide hydrolysis, for instance, induced by G-protein-coupled-receptor signaling. It plays an important role in neuronal development and function. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, May 2009]

TULP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0037992597).

BP6

Variant 12-2885388-C-T is Benign according to our data. Variant chr12-2885388-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 711715.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHNO1	NM_001252499.3 link	c.22C>T	p.Arg8Cys	missense_variant	Exon 2 of 3	ENST00000489288.7	NP_001239428.1	Q9BSD3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHNO1	ENST00000489288.7 link	c.22C>T	p.Arg8Cys	missense_variant	Exon 2 of 3	1	NM_001252499.3	ENSP00000438590.1		Q9BSD3-1

Frequencies

GnomAD3 genomes

AF:

0.00127

AC:

193

AN:

151916

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00373

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000526

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000567

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.000961

GnomAD3 exomes

AF:

0.000575

AC:

144

AN:

250544

Hom.:

AF XY:

0.000391

AC XY:

AN XY:

135436

show subpopulations

Gnomad AFR exome

AF:

0.00376

Gnomad AMR exome

AF:

0.000408

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000982

Gnomad FIN exome

AF:

0.000555

Gnomad NFE exome

AF:

0.000441

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000327

AC:

478

AN:

1461334

Hom.:

Cov.:

AF XY:

0.000303

AC XY:

220

AN XY:

726978

show subpopulations

Gnomad4 AFR exome

AF:

0.00404

Gnomad4 AMR exome

AF:

0.000404

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.000524

Gnomad4 NFE exome

AF:

0.000233

Gnomad4 OTH exome

AF:

0.000364

GnomAD4 genome

AF:

0.00128

AC:

195

AN:

152034

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

100

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.00376

Gnomad4 AMR

AF:

0.000525

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000567

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.000951

Alfa

AF:

0.000381

Hom.:

Bravo

AF:

0.00129

ESP6500AA

AF:

0.00386

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000610

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000415

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 05, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.091

.;.;T;T;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.59

T;T;T;.;T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.0038

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

.;N;N;N;.;.

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.5

D;D;.;D;D;D

REVEL

Benign

0.11

Sift

Benign

0.10

T;T;.;T;T;T

Sift4G

Benign

0.097

T;T;T;T;T;T

Polyphen

0.010

.;.;B;B;.;.

Vest4

0.17, 0.14, 0.16

MVP

0.048

MPC

0.11

ClinPred

0.019

GERP RS

-4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.058

gMVP

0.14

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