chr9-107306580-A-C

Variant names:

• chr9-107306580-A-C
• rs374011602
• NM_002874.5:c.430A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002874.5(RAD23B):​c.430A>C​(p.Lys144Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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. K144E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RAD23B NM_002874.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.599
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06109017).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD23B	NM_002874.5	MANE Select	c.430A>C	p.Lys144Gln	missense	Exon 4 of 10	NP_002865.1	P54727-1
	RAD23B	NM_001244713.1		c.367A>C	p.Lys123Gln	missense	Exon 4 of 10	NP_001231642.1	B7Z4W4
	RAD23B	NM_001244724.2		c.214A>C	p.Lys72Gln	missense	Exon 4 of 10	NP_001231653.1	P54727-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD23B	ENST00000358015.8	TSL:1 MANE Select	c.430A>C	p.Lys144Gln	missense	Exon 4 of 10	ENSP00000350708.3	P54727-1
	RAD23B	ENST00000416373.6	TSL:1	c.214A>C	p.Lys72Gln	missense	Exon 4 of 10	ENSP00000405623.2	P54727-2
	RAD23B	ENST00000866019.1		c.430A>C	p.Lys144Gln	missense	Exon 4 of 10	ENSP00000536078.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.88
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.60
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.030
Sift	Benign	0.57	T
Sift4G	Benign	0.49	T
Polyphen		0.0	B
Vest4		0.099
MutPred		0.27		Loss of ubiquitination at K144 (P = 0.0043)
MVP		0.46
MPC		0.48
ClinPred		0.10	T
GERP RS		0.62
PromoterAI		0.0014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.081
gMVP		0.17
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs374011602; hg19: chr9-110068861;