Variant 9-4834150-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_005772.5(RCL1):c.469C>T(p.Arg157Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,604,146 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

RCL1
NM_005772.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.29

Variant links:

Genes affected

RCL1 (HGNC:17687): (RNA terminal phosphate cyclase like 1) Predicted to enable endoribonuclease activity. Predicted to be involved in endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to act upstream of or within endonucleolytic cleavage in 5'-ETS of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) and endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to be located in nucleoplasm. Predicted to be active in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

RCL1 links:

Genome browser will be placed here

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
RCL1	NM_005772.5 linkuse as main transcript	c.469C>T	p.Arg157Trp	missense_variant	5/9	ENST00000381750.9
RCL1	NM_001286699.2 linkuse as main transcript	c.-6C>T		5_prime_UTR_variant	3/7
RCL1	NM_001286700.2 linkuse as main transcript	c.-6C>T		5_prime_UTR_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RCL1	ENST00000381750.9 linkuse as main transcript	c.469C>T	p.Arg157Trp	missense_variant	5/9	1	NM_005772.5	P1	Q9Y2P8-1
RCL1	ENST00000442869.5 linkuse as main transcript	c.-6C>T		5_prime_UTR_variant	4/8	3
RCL1	ENST00000473230.1 linkuse as main transcript	n.288+922C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000180

AC:

AN:

149962

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000320

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000265

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:

0.000119

Gnomad OTH

AF:

0.000972

GnomAD3 exomes

AF:

0.000156

AC:

AN:

250066

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

135138

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000585

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000331

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000107

AC:

155

AN:

1454066

Hom.:

Cov.:

AF XY:

0.0000995

AC XY:

AN XY:

723322

show subpopulations

Gnomad4 AFR exome

AF:

0.000330

Gnomad4 AMR exome

AF:

0.000590

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000236

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000948

Gnomad4 OTH exome

AF:

0.000150

GnomAD4 genome

AF:

0.000173

AC:

AN:

150080

Hom.:

Cov.:

AF XY:

0.000205

AC XY:

AN XY:

73276

show subpopulations

Gnomad4 AFR

AF:

0.000295

Gnomad4 AMR

AF:

0.000264

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000119

Gnomad4 OTH

AF:

0.000962

Alfa

AF:

0.000210

Hom.:

Bravo

AF:

0.000189

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000220

EpiControl

AF:

0.000178

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

Jan 03, 2024

The c.469C>T (p.R157W) alteration is located in exon 5 (coding exon 5) of the RCL1 gene. This alteration results from a C to T substitution at nucleotide position 469, causing the arginine (R) at amino acid position 157 to be replaced by a tryptophan (W). 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

Pathogenic

0.83

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.42

Cadd

Pathogenic

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.41

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Benign

0.66

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.099

MetaRNN

Uncertain

0.71

MetaSVM

Uncertain

0.39

MutationAssessor

Pathogenic

3.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-7.4

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.94

MVP

0.67

MPC

0.37

ClinPred

1.0

GERP RS

2.9

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.72

gMVP

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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