dbSNP rs781509755: RAD23B:p.Pro161Ala (chr9-107306631-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002874.5(RAD23B):c.481C>G(p.Pro161Ala) 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. 15/22 in silico tools predict 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. P161S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Consequence

RAD23B
NM_002874.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.98

Publications

0 publications found

Variant links:

Genes affected

RAD23B (HGNC:9813): (RAD23 homolog B, nucleotide excision repair protein) The protein encoded by this gene is one of two human homologs of Saccharomyces cerevisiae Rad23, a protein involved in the nucleotide excision repair (NER). This protein was found to be a component of the protein complex that specifically complements the NER defect of xeroderma pigmentosum group C (XP-c) cell extracts in vitro. This protein was also shown to interact with, and elevate the nucleotide excision activity of 3-methyladenine-DNA glycosylase (MPG), which suggested a role in DNA damage recognition in base excision repair. This protein contains an N-terminal ubiquitin-like domain, which was reported to interact with 26S proteasome, and thus this protein may be involved in the ubiquitin mediated proteolytic pathway in cells. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Sep 2011]

RAD23B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14883405).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002874.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAD23B	NM_002874.5	MANE Select	c.481C>G	p.Pro161Ala	missense	Exon 4 of 10	NP_002865.1	P54727-1
RAD23B	NM_001244713.1		c.418C>G	p.Pro140Ala	missense	Exon 4 of 10	NP_001231642.1	B7Z4W4
RAD23B	NM_001244724.2		c.265C>G	p.Pro89Ala	missense	Exon 4 of 10	NP_001231653.1	P54727-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAD23B	ENST00000358015.8	TSL:1 MANE Select	c.481C>G	p.Pro161Ala	missense	Exon 4 of 10	ENSP00000350708.3	P54727-1
RAD23B	ENST00000416373.6	TSL:1	c.265C>G	p.Pro89Ala	missense	Exon 4 of 10	ENSP00000405623.2	P54727-2
RAD23B	ENST00000866019.1		c.481C>G	p.Pro161Ala	missense	Exon 4 of 10	ENSP00000536078.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.23

Eigen

Benign

0.014

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.78

M_CAP

Benign

0.0077

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

4.0

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.95

REVEL

Benign

0.12

Sift

Benign

0.18

Sift4G

Benign

0.32

Polyphen

0.088

Vest4

0.46

MutPred

0.21

Loss of relative solvent accessibility (P = 0.0071)

MVP

0.32

MPC

0.46

ClinPred

0.54

GERP RS

5.6

PromoterAI

-0.015

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.095

gMVP

0.35

Mutation Taster

=67/33

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over