9-107322105-A-G

Position:

• chr9-107322105-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002874.5(RAD23B):​c.804A>G​(p.Thr268Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,606,918 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (4 hom.)
• Consequence: RAD23B NM_002874.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.178

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 Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 9-107322105-A-G is Benign according to our data. Variant chr9-107322105-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3039463.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.178 with no splicing effect.
• BS2: High AC in GnomAd4 at 332 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD23B	NM_002874.5	c.804A>G	p.Thr268Thr	synonymous_variant	7/10	ENST00000358015.8	NP_002865.1
RAD23B	NM_001244713.1	c.741A>G	p.Thr247Thr	synonymous_variant	7/10		NP_001231642.1
RAD23B	NM_001244724.2	c.588A>G	p.Thr196Thr	synonymous_variant	7/10		NP_001231653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD23B	ENST00000358015.8	c.804A>G	p.Thr268Thr	synonymous_variant	7/10	1	NM_002874.5	ENSP00000350708.3
RAD23B	ENST00000416373.6	c.588A>G	p.Thr196Thr	synonymous_variant	7/10	1		ENSP00000405623.2
RAD23B	ENST00000457811.1	c.288+3226A>G		intron_variant		3		ENSP00000396975.1

Frequencies

GnomAD3 genomes AF: 0.00219 AC: 333 AN: 152182 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00715

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00297

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00239 AC: 584 AN: 244680 Hom.: 2 AF XY: 0.00230 AC XY: 305 AN XY: 132366

Gnomad AFR exome AF: 0.000249

Gnomad AMR exome AF: 0.000249

Gnomad ASJ exome AF: 0.00294

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000205

Gnomad FIN exome AF: 0.00645

Gnomad NFE exome AF: 0.00348

Gnomad OTH exome AF: 0.00135

GnomAD4 exome AF: 0.00244 AC: 3547 AN: 1454618 Hom.: 4 Cov.: 31 AF XY: 0.00244 AC XY: 1762 AN XY: 723374

Gnomad4 AFR exome AF: 0.000331

Gnomad4 AMR exome AF: 0.000302

Gnomad4 ASJ exome AF: 0.00254

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000200

Gnomad4 FIN exome AF: 0.00686

Gnomad4 NFE exome AF: 0.00265

Gnomad4 OTH exome AF: 0.00216

GnomAD4 genome AF: 0.00218 AC: 332 AN: 152300 Hom.: 2 Cov.: 33 AF XY: 0.00216 AC XY: 161 AN XY: 74488

Gnomad4 AFR AF: 0.000602

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00404

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00715

Gnomad4 NFE AF: 0.00295

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00287 Hom.: 1

Bravo AF: 0.00153

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

RAD23B-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 16, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

RAD23B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.6
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4987014; hg19: chr9-110084386;