8-85217480-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001099673.3(RBIS):​c.20G>T​(p.Arg7Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000059 in 1,611,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

RBIS
NM_001099673.3 missense

Scores

1
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.626
Variant links:
Genes affected
RBIS (HGNC:32235): (ribosomal biogenesis factor) Involved in ribosome biogenesis. Located in cytosol; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.17111257).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RBISNM_001099673.3 linkc.20G>T p.Arg7Ile missense_variant Exon 2 of 4 ENST00000619594.5 NP_001093143.1 Q8N0T1-1A0A024R838

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RBISENST00000619594.5 linkc.20G>T p.Arg7Ile missense_variant Exon 2 of 4 1 NM_001099673.3 ENSP00000484492.1 Q8N0T1-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152104
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000281
AC:
7
AN:
248910
Hom.:
0
AF XY:
0.0000296
AC XY:
4
AN XY:
135030
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000532
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.0000631
AC:
92
AN:
1458980
Hom.:
0
Cov.:
29
AF XY:
0.0000675
AC XY:
49
AN XY:
725894
show subpopulations
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000792
Gnomad4 OTH exome
AF:
0.0000664
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152104
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74288
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000145
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.00000828
AC:
1
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 30, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.20G>T (p.R7I) alteration is located in exon 3 (coding exon 1) of the C8orf59 gene. This alteration results from a G to T substitution at nucleotide position 20, causing the arginine (R) at amino acid position 7 to be replaced by an isoleucine (I). 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
0.31
BayesDel_addAF
Benign
-0.071
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
19
DANN
Benign
0.95
DEOGEN2
Benign
0.12
T;T;T;T;T;T;T;.;.
Eigen
Benign
-0.55
Eigen_PC
Benign
-0.55
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Uncertain
0.94
.;.;.;.;D;.;D;D;D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.17
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.1
M;.;M;M;.;M;M;.;M
PROVEAN
Pathogenic
-5.6
.;.;.;.;D;.;.;D;D
REVEL
Benign
0.099
Sift
Uncertain
0.0030
.;.;.;.;D;.;.;D;D
Sift4G
Uncertain
0.0080
D;D;D;D;D;D;D;.;D
Vest4
0.41
MutPred
0.24
Loss of methylation at R7 (P = 0.0425);Loss of methylation at R7 (P = 0.0425);Loss of methylation at R7 (P = 0.0425);Loss of methylation at R7 (P = 0.0425);Loss of methylation at R7 (P = 0.0425);Loss of methylation at R7 (P = 0.0425);Loss of methylation at R7 (P = 0.0425);Loss of methylation at R7 (P = 0.0425);Loss of methylation at R7 (P = 0.0425);
MVP
0.048
ClinPred
0.79
D
GERP RS
0.45
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.062
gMVP
0.20

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: rs569231156; hg19: chr8-86129709; API