chr10-47353445-G-A

Variant summary

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

The NM_002900.3(RBP3):​c.3175G>A​(p.Val1059Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

RBP3
NM_002900.3 missense

Scores

1
1
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 5.04
Variant links:
Genes affected
RBP3 (HGNC:9921): (retinol binding protein 3) Interphotoreceptor retinol-binding protein is a large glycoprotein known to bind retinoids and found primarily in the interphotoreceptor matrix of the retina between the retinal pigment epithelium and the photoreceptor cells. It is thought to transport retinoids between the retinal pigment epithelium and the photoreceptors, a critical role in the visual process.The human IRBP gene is approximately 9.5 kbp in length and consists of four exons separated by three introns. The introns are 1.6-1.9 kbp long. The gene is transcribed by photoreceptor and retinoblastoma cells into an approximately 4.3-kilobase mRNA that is translated and processed into a glycosylated protein of 135,000 Da. The amino acid sequence of human IRBP can be divided into four contiguous homology domains with 33-38% identity, suggesting a series of gene duplication events. In the gene, the boundaries of these domains are not defined by exon-intron junctions, as might have been expected. The first three homology domains and part of the fourth are all encoded by the first large exon, which is 3,180 base pairs long. The remainder of the fourth domain is encoded in the last three exons, which are 191, 143, and approximately 740 base pairs long, respectively. [provided by RefSeq, Jul 2008]

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=0.14419404).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RBP3NM_002900.3 linkuse as main transcriptc.3175G>A p.Val1059Ile missense_variant 2/4 ENST00000584701.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RBP3ENST00000584701.2 linkuse as main transcriptc.3175G>A p.Val1059Ile missense_variant 2/41 NM_002900.3 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 26, 2020This sequence change replaces valine with isoleucine at codon 1059 of the RBP3 protein (p.Val1059Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with retinitis pigmentosa (PMID: 19074801). ClinVar contains an entry for this variant (Variation ID: 208324). This variant is not present in population databases (ExAC no frequency). -
Retinitis pigmentosa 66 Uncertain:1
Uncertain significance, no assertion criteria providedliterature onlyClinVar Staff, National Center for Biotechnology Information (NCBI)Jun 27, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_noAF
Pathogenic
0.42
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.073
T
LIST_S2
Benign
0.84
T
MetaRNN
Benign
0.14
T
Sift4G
Benign
0.34
T
Vest4
0.17
gMVP
0.76

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: rs864622002; hg19: chr10-48385917; API