Variant chr6-30345563-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024839.4(RPP21):c.231G>C(p.Gln77His) variant causes a missense change. The variant allele was found at a frequency of 0.24 in 1,538,976 control chromosomes in the GnomAD database, including 46,027 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.26 ( 5382 hom., cov: 27)

Exomes 𝑓: 0.24 ( 40645 hom. )

Consequence

RPP21
NM_024839.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.08

Variant links:

Genes affected

RPP21 (HGNC:21300): (ribonuclease P/MRP subunit p21) RPP21 is a protein subunit of nuclear ribonuclease P, which processes the 5-prime leader sequence of precursor tRNAs (Jarrous et al., 2001 [PubMed 11497433]).[supplied by OMIM, Jan 2009]

RPP21 links:

TRIM39-RPP21 (HGNC:):

TRIM39-RPP21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025838912).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RPP21	NM_024839.4 linkuse as main transcript	c.231G>C	p.Gln77His	missense_variant	3/5	ENST00000442966.7	NP_079115.1
TRIM39-RPP21	NM_001199119.1 linkuse as main transcript	c.1278G>C	p.Gln426His	missense_variant	8/10		NP_001186048.1
RPP21	NM_001199120.3 linkuse as main transcript	c.255G>C	p.Gln85His	missense_variant	3/5		NP_001186049.1
RPP21	NM_001199121.3 linkuse as main transcript	c.231G>C	p.Gln77His	missense_variant	3/5		NP_001186050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPP21	ENST00000442966.7 linkuse as main transcript	c.231G>C	p.Gln77His	missense_variant	3/5	1	NM_024839.4	ENSP00000403833	P1	Q9H633-1

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39523

AN:

150426

Hom.:

5382

Cov.:

show subpopulations

Gnomad AFR

AF:

0.337

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.218

Gnomad ASJ

AF:

0.344

Gnomad EAS

AF:

0.175

Gnomad SAS

AF:

0.362

Gnomad FIN

AF:

0.173

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.302

GnomAD3 exomes

AF:

0.239

AC:

42860

AN:

179358

Hom.:

5681

AF XY:

0.249

AC XY:

24133

AN XY:

96996

show subpopulations

Gnomad AFR exome

AF:

0.322

Gnomad AMR exome

AF:

0.156

Gnomad ASJ exome

AF:

0.355

Gnomad EAS exome

AF:

0.179

Gnomad SAS exome

AF:

0.366

Gnomad FIN exome

AF:

0.165

Gnomad NFE exome

AF:

0.231

Gnomad OTH exome

AF:

0.254

GnomAD4 exome

AF:

0.237

AC:

329143

AN:

1388430

Hom.:

40645

Cov.:

AF XY:

0.242

AC XY:

166622

AN XY:

687246

show subpopulations

Gnomad4 AFR exome

AF:

0.345

Gnomad4 AMR exome

AF:

0.167

Gnomad4 ASJ exome

AF:

0.370

Gnomad4 EAS exome

AF:

0.126

Gnomad4 SAS exome

AF:

0.371

Gnomad4 FIN exome

AF:

0.191

Gnomad4 NFE exome

AF:

0.226

Gnomad4 OTH exome

AF:

0.263

GnomAD4 genome

AF:

0.263

AC:

39522

AN:

150546

Hom.:

5382

Cov.:

AF XY:

0.261

AC XY:

19164

AN XY:

73504

show subpopulations

Gnomad4 AFR

AF:

0.337

Gnomad4 AMR

AF:

0.217

Gnomad4 ASJ

AF:

0.344

Gnomad4 EAS

AF:

0.175

Gnomad4 SAS

AF:

0.361

Gnomad4 FIN

AF:

0.173

Gnomad4 NFE

AF:

0.237

Gnomad4 OTH

AF:

0.299

Alfa

AF:

0.247

Hom.:

3614

Bravo

AF:

0.268

TwinsUK

AF:

0.219

AC:

812

ALSPAC

AF:

0.208

AC:

800

ESP6500AA

AF:

0.317

AC:

952

ESP6500EA

AF:

0.222

AC:

1197

ExAC

AF:

0.197

AC:

22176

Asia WGS

AF:

0.273

AC:

948

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

.;.;T;.;.

Eigen

Benign

0.081

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.93

MetaRNN

Benign

0.0026

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.4

.;.;L;.;L

MutationTaster

Benign

0.34

P;P;P;P

PROVEAN

Benign

-0.83

.;N;N;N;N

REVEL

Benign

0.040

Sift

Benign

0.46

.;T;T;T;T

Sift4G

Benign

0.061

T;T;T;T;T

Polyphen

0.24, 0.0040, 0.11

.;.;B;B;B

Vest4

0.14

MutPred

0.15

.;.;Gain of sheet (P = 0.0049);.;Gain of sheet (P = 0.0049);

MPC

0.50

ClinPred

0.032

GERP RS

4.7

Varity_R

0.44

gMVP

0.45

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over