Genetic Variant NM_002874.5:c.625G>A (chr9-107318823-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_002874.5(RAD23B):c.625G>A(p.Ala209Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,294 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. A209S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RAD23B
NM_002874.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.52

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4036563).

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.625G>A	p.Ala209Thr	missense	Exon 6 of 10	NP_002865.1	P54727-1
RAD23B	NM_001244713.1		c.562G>A	p.Ala188Thr	missense	Exon 6 of 10	NP_001231642.1	B7Z4W4
RAD23B	NM_001244724.2		c.409G>A	p.Ala137Thr	missense	Exon 6 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.625G>A	p.Ala209Thr	missense	Exon 6 of 10	ENSP00000350708.3	P54727-1
RAD23B	ENST00000416373.6	TSL:1	c.409G>A	p.Ala137Thr	missense	Exon 6 of 10	ENSP00000405623.2	P54727-2
RAD23B	ENST00000866019.1		c.625G>A	p.Ala209Thr	missense	Exon 6 of 10	ENSP00000536078.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461294

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726994

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111544

Other (OTH)

AF:

0.00

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.34

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.020

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.91

MutationAssessor

Pathogenic

3.2

PhyloP100

6.5

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.8

REVEL

Benign

0.16

Sift

Benign

0.10

Sift4G

Benign

0.38

Polyphen

0.98

Vest4

0.38

MutPred

0.37

Loss of helix (P = 0.2022)

MVP

0.53

MPC

1.0

ClinPred

0.95

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.29

gMVP

0.56

Mutation Taster

=48/52

disease causing

(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

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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