9-4793122-G-T

Variant names:

• chr9-4793122-G-T
• rs1842855925
• NM_005772.5:c.31G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005772.5(RCL1):​c.31G>T​(p.Ala11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RCL1 NM_005772.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.994

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.106143594).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCL1	NM_005772.5	c.31G>T	p.Ala11Ser	missense_variant	Exon 1 of 9	ENST00000381750.9	NP_005763.3
RCL1	NM_001286699.2	c.-196G>T		5_prime_UTR_variant	Exon 1 of 7		NP_001273628.1
RCL1	NM_001286700.2	c.-268G>T		5_prime_UTR_variant	Exon 1 of 8		NP_001273629.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCL1	ENST00000381750.9	c.31G>T	p.Ala11Ser	missense_variant	Exon 1 of 9	1	NM_005772.5	ENSP00000371169.4
RCL1	ENST00000381732.3	c.31G>T	p.Ala11Ser	missense_variant	Exon 1 of 3	2		ENSP00000371151.3
RCL1	ENST00000442869	c.-268G>T		5_prime_UTR_variant	Exon 1 of 8	3		ENSP00000412000.2
RCL1	ENST00000473230.1	n.36G>T		non_coding_transcript_exon_variant	Exon 1 of 4	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457904 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 725180

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: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.31G>T (p.A11S) alteration is located in exon 1 (coding exon 1) of the RCL1 gene. This alteration results from a G to T substitution at nucleotide position 31, causing the alanine (A) at amino acid position 11 to be replaced by a serine (S). 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	0.068
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Benign	0.91
DEOGEN2	Benign	0.0078	T;.
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.63	N;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.68	N;N
REVEL	Benign	0.061
Sift	Benign	0.37	T;T
Sift4G	Benign	0.44	T;T
Polyphen		0.0	B;.
Vest4		0.13
MutPred		0.47		Gain of glycosylation at A11 (P = 0.0436);Gain of glycosylation at A11 (P = 0.0436);
MVP		0.16
MPC		0.052
ClinPred		0.11	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.082
gMVP		0.44

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

Other links and lift over

dbSNP: rs1842855925; hg19: chr9-4793122;