rs1460301381

Variant names:

• chr9-4826926-C-A
• NM_005772.5:c.277C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-4826926-C-A
• chr9-4826926-C-G
• chr9-4826926-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_005772.5(RCL1):​c.277C>A​(p.Arg93Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R93C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RCL1 NM_005772.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.49

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

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.959

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCL1	NM_005772.5	c.277C>A	p.Arg93Ser	missense_variant	Exon 3 of 9	ENST00000381750.9	NP_005763.3
RCL1	NM_001286699.2	c.-90-6228C>A		intron_variant	Intron 1 of 6		NP_001273628.1
RCL1	NM_001286700.2	c.-91+3307C>A		intron_variant	Intron 2 of 7		NP_001273629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCL1	ENST00000381750.9	c.277C>A	p.Arg93Ser	missense_variant	Exon 3 of 9	1	NM_005772.5	ENSP00000371169.4
RCL1	ENST00000381732.3	c.277C>A	p.Arg93Ser	missense_variant	Exon 3 of 3	2		ENSP00000371151.3
RCL1	ENST00000442869.5	c.-91+3307C>A		intron_variant	Intron 2 of 7	3		ENSP00000412000.2
RCL1	ENST00000473230.1	n.213+3307C>A		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;.
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.96	D;D
MetaSVM	Uncertain	0.24	D
MutationAssessor	Pathogenic	3.3	M;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-5.5	D;D
REVEL	Pathogenic	0.76
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.042	D;D
Polyphen		1.0	D;.
Vest4		0.91
MutPred		0.81		Gain of catalytic residue at S90 (P = 0.0591);Gain of catalytic residue at S90 (P = 0.0591);
MVP		0.51
MPC		0.38
ClinPred		1.0	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.87
gMVP		0.91

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-4826926;