Variant chr10-90872018-C-T 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_006413.5(RPP30):c.32C>T(p.Ala11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,614,124 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 10 hom. )

Consequence

RPP30
NM_006413.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.315

Variant links:

Genes affected

RPP30 (HGNC:17688): (ribonuclease P/MRP subunit p30) Enables ribonuclease P RNA binding activity. Contributes to ribonuclease P activity. Involved in tRNA 5'-leader removal. Part of multimeric ribonuclease P complex and ribonuclease MRP complex. [provided by Alliance of Genome Resources, Apr 2022]

RPP30 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=0.0033192933).

BP6

Variant 10-90872018-C-T is Benign according to our data. Variant chr10-90872018-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2640672.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPP30	NM_006413.5 linkuse as main transcript	c.32C>T	p.Ala11Val	missense_variant	1/11	ENST00000371703.8	NP_006404.1
RPP30	NM_001104546.2 linkuse as main transcript	c.32C>T	p.Ala11Val	missense_variant	1/14		NP_001098016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPP30	ENST00000371703.8 linkuse as main transcript	c.32C>T	p.Ala11Val	missense_variant	1/11	1	NM_006413.5	ENSP00000360768	P1	P78346-1
RPP30	ENST00000413330.5 linkuse as main transcript	c.32C>T	p.Ala11Val	missense_variant	1/13	5		ENSP00000389182		P78346-2
RPP30	ENST00000277882.7 linkuse as main transcript	c.32C>T	p.Ala11Val	missense_variant	1/10	5		ENSP00000277882
RPP30	ENST00000487998.5 linkuse as main transcript	n.46C>T		non_coding_transcript_exon_variant	1/10	5

Frequencies

GnomAD3 genomes

AF:

0.00136

AC:

207

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00190

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00193

AC:

485

AN:

251364

Hom.:

AF XY:

0.00203

AC XY:

276

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.00427

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00183

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.00242

Gnomad OTH exome

AF:

0.00423

GnomAD4 exome

AF:

0.00173

AC:

2522

AN:

1461808

Hom.:

Cov.:

AF XY:

0.00182

AC XY:

1322

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.00237

Gnomad4 ASJ exome

AF:

0.00394

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00219

Gnomad4 FIN exome

AF:

0.000356

Gnomad4 NFE exome

AF:

0.00166

Gnomad4 OTH exome

AF:

0.00247

GnomAD4 genome

AF:

0.00136

AC:

207

AN:

152316

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

105

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00190

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00209

Hom.:

Bravo

AF:

0.00142

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00192

AC:

233

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00349

EpiControl

AF:

0.00415

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

Mar 01, 2023

RPP30: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

6.7

DANN

Benign

0.91

DEOGEN2

Benign

0.093

T;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.61

T;T;T

M_CAP

Benign

0.0088

MetaRNN

Benign

0.0033

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.56

N;N;N

REVEL

Benign

0.056

Sift

Benign

0.50

T;T;T

Sift4G

Benign

0.47

T;T;T

Polyphen

0.38

B;.;.

Vest4

0.12

MVP

0.22

MPC

0.020

ClinPred

0.0066

GERP RS

-2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.091

gMVP

0.46

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