rs1566266741

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001268.4(RCBTB2):​c.1378G>T​(p.Ala460Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. A460T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

RCBTB2
NM_001268.4 missense

Scores

6
10
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.47
Variant links:
Genes affected
RCBTB2 (HGNC:1914): (RCC1 and BTB domain containing protein 2) This gene encodes a protein containing two C-terminal BTB/POZ domains that is related to regulator of chromosome condensation (RCC). The encoded protein may act as a guanine nucleotide exchange factor. This gene is observed to be lost or underexpressed in prostate cancers. There is a pseudogene of this gene on chromosome 10. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]
RB1 (HGNC:9884): (RB transcriptional corepressor 1) The protein encoded by this gene is a negative regulator of the cell cycle and was the first tumor suppressor gene found. The encoded protein also stabilizes constitutive heterochromatin to maintain the overall chromatin structure. The active, hypophosphorylated form of the protein binds transcription factor E2F1. Defects in this gene are a cause of childhood cancer retinoblastoma (RB), bladder cancer, and osteogenic sarcoma. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.778

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RCBTB2NM_001268.4 linkc.1378G>T p.Ala460Ser missense_variant Exon 13 of 15 ENST00000344532.8 NP_001259.1 O95199-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RCBTB2ENST00000344532.8 linkc.1378G>T p.Ala460Ser missense_variant Exon 13 of 15 1 NM_001268.4 ENSP00000345144.3 O95199-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.49
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.030
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.36
T;T;.;.
Eigen
Pathogenic
0.69
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D;D;D;D
M_CAP
Uncertain
0.16
D
MetaRNN
Pathogenic
0.78
D;D;D;D
MetaSVM
Uncertain
0.049
D
MutationAssessor
Uncertain
2.7
M;.;.;.
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-1.9
N;N;N;.
REVEL
Uncertain
0.44
Sift
Uncertain
0.017
D;D;D;.
Sift4G
Uncertain
0.0060
D;D;D;D
Polyphen
0.73
P;D;P;.
Vest4
0.74
MutPred
0.66
.;.;Gain of disorder (P = 0.0229);.;
MVP
0.85
MPC
0.18
ClinPred
0.96
D
GERP RS
5.1
Varity_R
0.40
gMVP
0.59

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: rs1566266741; hg19: chr13-49073763; API