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GeneBe

9-4849515-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005772.5(RCL1):c.936T>C(p.Val312=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,613,888 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0085 ( 10 hom., cov: 32)
Exomes 𝑓: 0.010 ( 89 hom. )

Consequence

RCL1
NM_005772.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.28
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-4849515-T-C is Benign according to our data. Variant chr9-4849515-T-C is described in ClinVar as [Benign]. Clinvar id is 789301.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.28 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 10 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RCL1NM_005772.5 linkuse as main transcriptc.936T>C p.Val312= synonymous_variant 8/9 ENST00000381750.9
RCL1NM_001286699.2 linkuse as main transcriptc.462T>C p.Val154= synonymous_variant 6/7
RCL1NM_001286700.2 linkuse as main transcriptc.462T>C p.Val154= synonymous_variant 7/8
RCL1NM_001286701.2 linkuse as main transcriptc.378T>C p.Val126= synonymous_variant 4/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RCL1ENST00000381750.9 linkuse as main transcriptc.936T>C p.Val312= synonymous_variant 8/91 NM_005772.5 P1Q9Y2P8-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00847
AC:
1288
AN:
152034
Hom.:
10
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00244
Gnomad AMI
AF:
0.0121
Gnomad AMR
AF:
0.0149
Gnomad ASJ
AF:
0.0202
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00104
Gnomad FIN
AF:
0.00858
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0112
Gnomad OTH
AF:
0.0101
GnomAD3 exomes
AF:
0.00842
AC:
2118
AN:
251450
Hom.:
15
AF XY:
0.00854
AC XY:
1161
AN XY:
135906
show subpopulations
Gnomad AFR exome
AF:
0.00178
Gnomad AMR exome
AF:
0.0100
Gnomad ASJ exome
AF:
0.0146
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00183
Gnomad FIN exome
AF:
0.00905
Gnomad NFE exome
AF:
0.0111
Gnomad OTH exome
AF:
0.0124
GnomAD4 exome
AF:
0.0103
AC:
15113
AN:
1461734
Hom.:
89
Cov.:
31
AF XY:
0.0102
AC XY:
7414
AN XY:
727176
show subpopulations
Gnomad4 AFR exome
AF:
0.00170
Gnomad4 AMR exome
AF:
0.00946
Gnomad4 ASJ exome
AF:
0.0137
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00185
Gnomad4 FIN exome
AF:
0.00878
Gnomad4 NFE exome
AF:
0.0117
Gnomad4 OTH exome
AF:
0.0101
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00846
AC:
1287
AN:
152154
Hom.:
10
Cov.:
32
AF XY:
0.00855
AC XY:
636
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.00243
Gnomad4 AMR
AF:
0.0149
Gnomad4 ASJ
AF:
0.0202
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00858
Gnomad4 NFE
AF:
0.0112
Gnomad4 OTH
AF:
0.00995
Alfa
AF:
0.0103
Hom.:
4
Bravo
AF:
0.00818
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.0124
EpiControl
AF:
0.0126

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeApr 23, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
Cadd
Benign
7.1
Dann
Benign
0.77

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.

Other links and lift over

dbSNP: rs35815255; hg19: chr9-4849515; COSMIC: COSV100762122; COSMIC: COSV100762122; API