12-2887992-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_001252499.3(RHNO1):c.250C>T(p.Arg84*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,613,754 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 5 hom. )

Consequence

RHNO1
NM_001252499.3 stop_gained

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.16

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

ciliopathy
Inheritance: AR Classification: STRONG Submitted by: ClinGen
hepatorenocardiac degenerative fibrosis
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

TULP3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP6

Variant 12-2887992-C-T is Benign according to our data. Variant chr12-2887992-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 717229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001252499.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RHNO1	NM_001252499.3	MANE Select	c.250C>T	p.Arg84*	stop_gained	Exon 3 of 3	NP_001239428.1	Q9BSD3-1
RHNO1	NM_001257097.2		c.250C>T	p.Arg84*	stop_gained	Exon 3 of 3	NP_001244026.1	Q9BSD3-1
RHNO1	NM_001257098.2		c.250C>T	p.Arg84*	stop_gained	Exon 3 of 3	NP_001244027.1	Q9BSD3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RHNO1	ENST00000489288.7	TSL:1 MANE Select	c.250C>T	p.Arg84*	stop_gained	Exon 3 of 3	ENSP00000438590.1	Q9BSD3-1
RHNO1	ENST00000618250.4	TSL:4	c.250C>T	p.Arg84*	stop_gained	Exon 3 of 3	ENSP00000479598.1	Q9BSD3-1
RHNO1	ENST00000461997.5	TSL:2	c.208C>T	p.Arg70*	stop_gained	Exon 3 of 3	ENSP00000438828.1	Q9BSD3-2

Frequencies

GnomAD3 genomes

AF:

0.00167

AC:

253

AN:

151836

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000508

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000394

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00635

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00229

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00133

AC:

334

AN:

251334

AF XY:

0.00127

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00425

Gnomad NFE exome

AF:

0.00198

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.00227

AC:

3312

AN:

1461802

Hom.:

Cov.:

AF XY:

0.00221

AC XY:

1605

AN XY:

727188

show subpopulations

African (AFR)

AF:

0.000418

AC:

AN:

33480

American (AMR)

AF:

0.000224

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000174

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00438

AC:

234

AN:

53418

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00262

AC:

2911

AN:

1111960

Other (OTH)

AF:

0.00207

AC:

125

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

164

328

493

657

821

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00167

AC:

253

AN:

151952

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

124

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.000507

AC:

AN:

41420

American (AMR)

AF:

0.000393

AC:

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00635

AC:

AN:

10550

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00229

AC:

156

AN:

67988

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00165

Hom.:

Bravo

AF:

0.00113

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00123

AC:

149

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00169

EpiControl

AF:

0.00172

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Pathogenic

0.42

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.011

FATHMM_MKL

Uncertain

0.82

PhyloP100

2.2

Vest4

0.15

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=55/145

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over