chr9-107323995-G-C

Variant names:

• chr9-107323995-G-C
• rs140228782
• NM_002874.5:c.923G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002874.5(RAD23B):​c.923G>C​(p.Arg308Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAD23B NM_002874.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.76

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD23B	NM_002874.5	c.923G>C	p.Arg308Pro	missense_variant	Exon 8 of 10	ENST00000358015.8	NP_002865.1
RAD23B	NM_001244713.1	c.860G>C	p.Arg287Pro	missense_variant	Exon 8 of 10		NP_001231642.1
RAD23B	NM_001244724.2	c.707G>C	p.Arg236Pro	missense_variant	Exon 8 of 10		NP_001231653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD23B	ENST00000358015.8	c.923G>C	p.Arg308Pro	missense_variant	Exon 8 of 10	1	NM_002874.5	ENSP00000350708.3
RAD23B	ENST00000416373.6	c.707G>C	p.Arg236Pro	missense_variant	Exon 8 of 10	1		ENSP00000405623.2
RAD23B	ENST00000457811.1	c.288+5116G>C		intron_variant	Intron 3 of 3	3		ENSP00000396975.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T;.
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.5	N;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0060	D;D
Sift4G	Benign	0.17	T;T
Polyphen		0.75	P;.
Vest4		0.70
MutPred		0.51		Gain of glycosylation at R308 (P = 0.0348);.;
MVP		0.71
MPC		1.0
ClinPred		0.88	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.76
gMVP		0.85

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

Other links and lift over

dbSNP: rs140228782; hg19: chr9-110086276;