Variant 3-51936280-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004704.5(RRP9):c.712A>C(p.Thr238Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0105 in 1,613,900 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0077 ( 9 hom., cov: 33)

Exomes 𝑓: 0.011 ( 112 hom. )

Consequence

RRP9
NM_004704.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.44

Variant links:

Genes affected

RRP9 (HGNC:16829): (ribosomal RNA processing 9, U3 small nucleolar RNA binding protein) This gene encodes a member of the WD-repeat protein family. The encoded protein is a component of the nucleolar small nuclear ribonucleoprotein particle (snoRNP) and is essential for 18s rRNA processing during ribosome synthesis. It contains seven WD domains required for nucleolar localization and specific interaction with the U3 small nucleolar RNA (U3 snoRNA). [provided by RefSeq, Oct 2012]

RRP9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013536215).

BP6

Variant 3-51936280-T-G is Benign according to our data. Variant chr3-51936280-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2653873.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 1169 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRP9	NM_004704.5 linkuse as main transcript	c.712A>C	p.Thr238Pro	missense_variant	8/15	ENST00000232888.7	NP_004695.1	O43818
RRP9	XM_047449172.1 linkuse as main transcript	c.580A>C	p.Thr194Pro	missense_variant	8/15		XP_047305128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRP9	ENST00000232888.7 linkuse as main transcript	c.712A>C	p.Thr238Pro	missense_variant	8/15	1	NM_004704.5	ENSP00000232888.6		O43818

Frequencies

GnomAD3 genomes

AF:

0.00770

AC:

1170

AN:

151924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00714

Gnomad ASJ

AF:

0.0162

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00853

Gnomad FIN

AF:

0.0148

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0102

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00793

AC:

1994

AN:

251480

Hom.:

AF XY:

0.00795

AC XY:

1081

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00215

Gnomad AMR exome

AF:

0.00532

Gnomad ASJ exome

AF:

0.0123

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00781

Gnomad FIN exome

AF:

0.0126

Gnomad NFE exome

AF:

0.00957

Gnomad OTH exome

AF:

0.00815

GnomAD4 exome

AF:

0.0108

AC:

15763

AN:

1461858

Hom.:

112

Cov.:

AF XY:

0.0107

AC XY:

7746

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00149

Gnomad4 AMR exome

AF:

0.00555

Gnomad4 ASJ exome

AF:

0.0130

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00854

Gnomad4 FIN exome

AF:

0.0133

Gnomad4 NFE exome

AF:

0.0117

Gnomad4 OTH exome

AF:

0.0107

GnomAD4 genome

AF:

0.00769

AC:

1169

AN:

152042

Hom.:

Cov.:

AF XY:

0.00732

AC XY:

544

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.00217

Gnomad4 AMR

AF:

0.00713

Gnomad4 ASJ

AF:

0.0162

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00853

Gnomad4 FIN

AF:

0.0148

Gnomad4 NFE

AF:

0.0102

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.00850

Hom.:

Bravo

AF:

0.00647

TwinsUK

AF:

0.0127

AC:

ALSPAC

AF:

0.0119

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.0112

AC:

ExAC

AF:

0.00742

AC:

901

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00845

EpiControl

AF:

0.00853

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

RRP9: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.057

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.81

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.4

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.9

REVEL

Benign

0.27

Sift

Uncertain

0.029

Sift4G

Benign

0.079

Polyphen

0.99

Vest4

0.59

MVP

0.72

MPC

1.4

ClinPred

0.020

GERP RS

5.2

Varity_R

0.88

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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