rs1244948800

Variant names:

• chr9-107300187-C-A
• NM_002874.5:c.113C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-107300187-C-A
• chr9-107300187-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002874.5(RAD23B):​c.113C>A​(p.Ala38Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,234 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RAD23B NM_002874.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34377873).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD23B	NM_002874.5	c.113C>A	p.Ala38Asp	missense_variant	Exon 2 of 10	ENST00000358015.8	NP_002865.1
RAD23B	NM_001244713.1	c.50C>A	p.Ala17Asp	missense_variant	Exon 2 of 10		NP_001231642.1
RAD23B	NM_001244724.2	c.-104C>A		5_prime_UTR_variant	Exon 2 of 10		NP_001231653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD23B	ENST00000358015.8	c.113C>A	p.Ala38Asp	missense_variant	Exon 2 of 10	1	NM_002874.5	ENSP00000350708.3
RAD23B	ENST00000416373	c.-104C>A		5_prime_UTR_variant	Exon 2 of 10	1		ENSP00000405623.2
RAD23B	ENST00000419616.5	c.113C>A	p.Ala38Asp	missense_variant	Exon 3 of 5	3		ENSP00000416868.1
RAD23B	ENST00000442587.1	c.50C>A	p.Ala17Asp	missense_variant	Exon 2 of 4	2		ENSP00000415821.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456234 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724306

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: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	.;T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.4	.;L;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Benign	0.19
Sift	Uncertain	0.012	D;D;D
Sift4G	Benign	0.52	T;T;T
Polyphen		0.98	.;D;.
Vest4		0.47
MutPred		0.36		Loss of methylation at K36 (P = 0.0554);Loss of methylation at K36 (P = 0.0554);.;
MVP		0.40
MPC		0.67
ClinPred		0.66	D
GERP RS		5.7
Varity_R		0.35
gMVP		0.69

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-110062468;