9-4834394-A-T

Variant names:

• chr9-4834394-A-T
• rs457287
• NM_005772.5:c.584+129A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005772.5(RCL1):​c.584+129A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RCL1 NM_005772.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 11 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005772.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCL1	NM_005772.5	MANE Select	c.584+129A>T		intron	N/A	NP_005763.3
	RCL1	NM_001286699.2		c.110+129A>T		intron	N/A	NP_001273628.1
	RCL1	NM_001286700.2		c.110+129A>T		intron	N/A	NP_001273629.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCL1	ENST00000381750.9	TSL:1 MANE Select	c.584+129A>T		intron	N/A	ENSP00000371169.4
	RCL1	ENST00000442869.5	TSL:3	c.110+129A>T		intron	N/A	ENSP00000412000.2
	RCL1	ENST00000473230.1	TSL:3	n.288+1166A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 906416 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 452082

African (AFR) AF: 0.00 AC: 0 AN: 19898

American (AMR) AF: 0.00 AC: 0 AN: 20950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15328

East Asian (EAS) AF: 0.00 AC: 0 AN: 27146

South Asian (SAS) AF: 0.00 AC: 0 AN: 55850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2648

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 700136

Other (OTH) AF: 0.00 AC: 0 AN: 38426

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 111648

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.79
PhyloP100		-0.018

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

Other links and lift over

dbSNP: rs457287; hg19: chr9-4834394;