20-17615483-C-T

Variant summary

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

The NM_001365613.2(RRBP1):​c.3998G>A​(p.Arg1333His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,455,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. R1333L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

RRBP1
NM_001365613.2 missense

Scores

9
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.45
Variant links:
Genes affected
RRBP1 (HGNC:10448): (ribosome binding protein 1) This gene encodes a ribosome-binding protein of the endoplasmic reticulum (ER) membrane. Studies suggest that this gene plays a role in ER proliferation, secretory pathways and secretory cell differentiation, and mediation of ER-microtubule interactions. Alternative splicing has been observed and protein isoforms are characterized by regions of N-terminal decapeptide and C-terminal heptad repeats. Splicing of the tandem repeats results in variations in ribosome-binding affinity and secretory function. The full-length nature of variants which differ in repeat length has not been determined. Pseudogenes of this gene have been identified on chromosomes 3 and 7, and RRBP1 has been excluded as a candidate gene in the cause of Alagille syndrome, the result of a mutation in a nearby gene on chromosome 20p12. [provided by RefSeq, Apr 2012]

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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=0.25053465).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RRBP1NM_001365613.2 linkc.3998G>A p.Arg1333His missense_variant Exon 23 of 25 ENST00000377813.6 NP_001352542.1
RRBP1NM_001042576.2 linkc.2699G>A p.Arg900His missense_variant Exon 24 of 26 NP_001036041.2 Q9P2E9-3
RRBP1NM_004587.3 linkc.2699G>A p.Arg900His missense_variant Exon 23 of 25 NP_004578.3 Q9P2E9-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RRBP1ENST00000377813.6 linkc.3998G>A p.Arg1333His missense_variant Exon 23 of 25 1 NM_001365613.2 ENSP00000367044.1 Q9P2E9-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000821
AC:
2
AN:
243676
Hom.:
0
AF XY:
0.00000756
AC XY:
1
AN XY:
132222
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:
0.0000676
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000412
AC:
6
AN:
1455322
Hom.:
0
Cov.:
31
AF XY:
0.00000414
AC XY:
3
AN XY:
724014
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:
0.0000470
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000333
GnomAD4 genome
Cov.:
33
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.088
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.10
.;.;T;T;.;.;T
Eigen
Uncertain
0.46
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.86
D;D;D;.;D;.;D
M_CAP
Benign
0.048
D
MetaRNN
Benign
0.25
T;T;T;T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Uncertain
2.5
.;.;M;M;.;.;.
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-1.8
.;.;N;N;N;N;N
REVEL
Benign
0.18
Sift
Uncertain
0.0050
.;.;D;D;D;D;D
Sift4G
Uncertain
0.028
D;D;T;T;D;D;D
Polyphen
1.0, 1.0
.;.;D;D;D;D;.
Vest4
0.23
MVP
0.54
MPC
0.41
ClinPred
0.91
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.099
gMVP
0.10

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: rs368160955; hg19: chr20-17596128; API