Variant 21-43797922-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003683.6(RRP1):c.633C>A(p.Asn211Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000762 in 1,613,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

RRP1
NM_003683.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.37

Variant links:

Genes affected

RRP1 (HGNC:18785): (ribosomal RNA processing 1) The protein encoded by this gene is the putative homolog of the yeast ribosomal RNA processing protein RRP1. The encoded protein is involved in the late stages of nucleologenesis at the end of mitosis, and may be required for the generation of 28S rRNA. [provided by RefSeq, Jul 2008]

RRP1 links:

RRP1 (HGNC:):

RRP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0752632).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRP1	NM_003683.6 linkuse as main transcript	c.633C>A	p.Asn211Lys	missense_variant	8/13	ENST00000497547.2	NP_003674.1	P56182
RRP1	XM_017028485.3 linkuse as main transcript	c.633C>A	p.Asn211Lys	missense_variant	8/13		XP_016883974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRP1	ENST00000497547.2 linkuse as main transcript	c.633C>A	p.Asn211Lys	missense_variant	8/13	1	NM_003683.6	ENSP00000417464.1		P56182

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000522

AC:

AN:

248946

Hom.:

AF XY:

0.0000592

AC XY:

AN XY:

135064

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000787

AC:

115

AN:

1461578

Hom.:

Cov.:

AF XY:

0.0000811

AC XY:

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000998

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000724

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:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000360

Hom.:

Bravo

AF:

0.0000491

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000238

AC:

ExAC

AF:

0.0000909

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 25, 2024

The c.633C>A (p.N211K) alteration is located in exon 8 (coding exon 8) of the RRP1 gene. This alteration results from a C to A substitution at nucleotide position 633, causing the asparagine (N) at amino acid position 211 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.5

DANN

Benign

0.56

DEOGEN2

Benign

0.0039

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.65

M_CAP

Benign

0.0037

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.27

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.73

REVEL

Benign

0.082

Sift4G

Benign

0.56

Polyphen

0.68

Vest4

0.14

MutPred

0.53

Gain of MoRF binding (P = 0.0271);

MVP

0.28

MPC

0.18

ClinPred

0.040

GERP RS

-2.6

Varity_R

0.23

gMVP

0.083

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over