Genetic Variant NM_002874.5:c.382C>A (chr9-107306532-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002874.5(RAD23B):c.382C>A(p.Pro128Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RAD23B
NM_002874.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.84

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3615529).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD23B	NM_002874.5 link	c.382C>A	p.Pro128Thr	missense_variant	Exon 4 of 10	ENST00000358015.8	NP_002865.1	P54727-1
RAD23B	NM_001244713.1 link	c.319C>A	p.Pro107Thr	missense_variant	Exon 4 of 10		NP_001231642.1	B7Z4W4
RAD23B	NM_001244724.2 link	c.166C>A	p.Pro56Thr	missense_variant	Exon 4 of 10		NP_001231653.1	P54727-2B7Z4W4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD23B	ENST00000358015.8 link	c.382C>A	p.Pro128Thr	missense_variant	Exon 4 of 10	1	NM_002874.5	ENSP00000350708.3		P54727-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Uncertain

0.095

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.40

.;T;.

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.9

.;L;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.19

Sift

Uncertain

0.0050

D;T;D

Sift4G

Benign

0.34

T;T;T

Polyphen

1.0

.;D;.

Vest4

0.55, 0.40

MutPred

0.24

Gain of glycosylation at P128 (P = 0.0131);Gain of glycosylation at P128 (P = 0.0131);.;

MVP

0.66

MPC

0.50

ClinPred

0.55

GERP RS

5.7

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.085

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over