Variant 9-4793188-C-G 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.97C>G(p.Arg33Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,200 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Consequence

RCL1
NM_005772.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.18

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:

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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
RCL1	NM_005772.5 linkuse as main transcript	c.97C>G	p.Arg33Gly	missense_variant	1/9	ENST00000381750.9
RCL1	NM_001286699.2 linkuse as main transcript	c.-130C>G		5_prime_UTR_variant	1/7
RCL1	NM_001286700.2 linkuse as main transcript	c.-202C>G		5_prime_UTR_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RCL1	ENST00000381750.9 linkuse as main transcript	c.97C>G	p.Arg33Gly	missense_variant	1/9	1	NM_005772.5	P1	Q9Y2P8-1
RCL1	ENST00000381732.3 linkuse as main transcript	c.97C>G	p.Arg33Gly	missense_variant	1/3	2
RCL1	ENST00000442869.5 linkuse as main transcript	c.-202C>G		5_prime_UTR_variant	1/8	3
RCL1	ENST00000473230.1 linkuse as main transcript	n.102C>G		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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

Dec 19, 2023

The c.97C>G (p.R33G) alteration is located in exon 1 (coding exon 1) of the RCL1 gene. This alteration results from a C to G substitution at nucleotide position 97, causing the arginine (R) at amino acid position 33 to be replaced by a glycine (G). 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

0.19

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.15

T;.

Eigen

Benign

0.035

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.051

MetaRNN

Uncertain

0.51

D;D

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.4

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-2.6

D;N

REVEL

Benign

0.17

Sift

Benign

0.35

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.095

B;.

Vest4

0.66

MutPred

0.46

Loss of MoRF binding (P = 0.0411);Loss of MoRF binding (P = 0.0411);

MVP

0.36

MPC

0.088

ClinPred

0.95

GERP RS

5.5

Varity_R

0.43

gMVP

0.72

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