Variant 11-6601150-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4BP6_Moderate

The NM_015324.4(RRP8):c.916C>T(p.Arg306Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,613,568 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 1 hom. )

Consequence

RRP8
NM_015324.4 missense, splice_region

Scores

Splicing: ADA: 0.001557

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.72

Variant links:

Genes affected

RRP8 (HGNC:29030): (ribosomal RNA processing 8) Enables methylated histone binding activity. Involved in several processes, including cellular response to glucose starvation; intrinsic apoptotic signaling pathway by p53 class mediator; and regulation of gene expression. Located in several cellular components, including cytosol; nuclear lumen; and rDNA heterochromatin. Part of chromatin silencing complex. [provided by Alliance of Genome Resources, Apr 2022]

RRP8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26743287).

BP6

Variant 11-6601150-G-A is Benign according to our data. Variant chr11-6601150-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2641556.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRP8	NM_015324.4 linkuse as main transcript	c.916C>T	p.Arg306Trp	missense_variant, splice_region_variant	3/7	ENST00000254605.11	NP_056139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RRP8	ENST00000254605.11 linkuse as main transcript	c.916C>T	p.Arg306Trp	missense_variant, splice_region_variant	3/7	1	NM_015324.4	ENSP00000254605	P1
RRP8	ENST00000534343.1 linkuse as main transcript	c.100-375C>T		intron_variant		2		ENSP00000436960
RRP8	ENST00000526352.5 linkuse as main transcript	n.155C>T		non_coding_transcript_exon_variant	1/3	2
RRP8	ENST00000533907.1 linkuse as main transcript	c.916C>T	p.Arg306Trp	missense_variant, NMD_transcript_variant	3/5	5		ENSP00000436246

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

250424

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135384

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1461382

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

726948

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000330

AC:

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

RRP8: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.092

Eigen

Benign

0.078

Eigen_PC

Benign

0.049

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.029

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.24

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.024

Polyphen

1.0

Vest4

0.36

MutPred

0.55

Gain of loop (P = 0.024);

MVP

0.39

MPC

0.021

ClinPred

0.43

GERP RS

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.77

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0016

dbscSNV1_RF

Benign

0.31

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