Variant chr21-43789675-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003683.6(RRP1):c.46C>T(p.Arg16Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000352 in 1,421,928 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

RRP1
NM_003683.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.631

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRP1	NM_003683.6 linkuse as main transcript	c.46C>T	p.Arg16Cys	missense_variant	1/13	ENST00000497547.2	NP_003674.1	P56182
RRP1	XM_017028485.3 linkuse as main transcript	c.46C>T	p.Arg16Cys	missense_variant	1/13		XP_016883974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RRP1	ENST00000497547.2 linkuse as main transcript	c.46C>T	p.Arg16Cys	missense_variant	1/13	1	NM_003683.6	ENSP00000417464.1	P56182
RRP1	ENST00000475534.5 linkuse as main transcript	n.163C>T		non_coding_transcript_exon_variant	1/6	3
RRP1	ENST00000483896.5 linkuse as main transcript	n.46C>T		non_coding_transcript_exon_variant	1/9	3		ENSP00000426898.1	D6RE82
RRP1	ENST00000492638.1 linkuse as main transcript	n.99C>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000352

AC:

AN:

1421928

Hom.:

Cov.:

AF XY:

0.00000284

AC XY:

AN XY:

704532

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000366

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 27, 2024

The c.46C>T (p.R16C) alteration is located in exon 1 (coding exon 1) of the RRP1 gene. This alteration results from a C to T substitution at nucleotide position 46, causing the arginine (R) at amino acid position 16 to be replaced by a cysteine (C). 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

Uncertain

0.54

BayesDel_addAF

Uncertain

0.053

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.086

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.50

LIST_S2

Pathogenic

0.97

M_CAP

Pathogenic

0.47

MetaRNN

Uncertain

0.57

MetaSVM

Benign

-0.34

MutationAssessor

Pathogenic

3.3

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-6.1

REVEL

Uncertain

0.42

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.36

MutPred

0.66

Loss of MoRF binding (P = 0.0132);

MVP

0.56

MPC

0.74

ClinPred

1.0

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.95

gMVP

0.42

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