19-12948547-C-A

Variant names:

• chr19-12948547-C-A
• rs1030984404
• NM_005053.4:c.467C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005053.4(RAD23A):​c.467C>A​(p.Thr156Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000694 in 1,441,902 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T156M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: RAD23A NM_005053.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.27
• Publications: 0 publications found

Genes affected

RAD23A (HGNC:9812): (RAD23 homolog A, nucleotide excision repair protein) The protein encoded by this gene is one of two human homologs of Saccharomyces cerevisiae Rad23, a protein involved in nucleotide excision repair. Proteins in this family have a modular domain structure consisting of an ubiquitin-like domain (UbL), ubiquitin-associated domain 1 (UbA1), XPC-binding domain and UbA2. The protein encoded by this gene plays an important role in nucleotide excision repair and also in delivery of polyubiquitinated proteins to the proteasome. Alternative splicing results in multiple transcript variants encoding multiple isoforms. [provided by RefSeq, Jun 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005053.4. 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
	RAD23A	NM_005053.4	MANE Select	c.467C>A	p.Thr156Lys	missense	Exon 4 of 9	NP_005044.1	P54725-1
	RAD23A	NM_001270362.2		c.467C>A	p.Thr156Lys	missense	Exon 4 of 9	NP_001257291.1	P54725-3
	RAD23A	NM_001270363.2		c.467C>A	p.Thr156Lys	missense	Exon 4 of 8	NP_001257292.1	P54725-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD23A	ENST00000586534.6	TSL:1 MANE Select	c.467C>A	p.Thr156Lys	missense	Exon 4 of 9	ENSP00000467024.1	P54725-1
	RAD23A	ENST00000316856.7	TSL:1	c.467C>A	p.Thr156Lys	missense	Exon 4 of 9	ENSP00000321365.3	P54725-3
	RAD23A	ENST00000875551.1		c.461C>A	p.Thr154Lys	missense	Exon 4 of 9	ENSP00000545610.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000694 AC: 10 AN: 1441902 Hom.: 0 Cov.: 32 AF XY: 0.00000559 AC XY: 4 AN XY: 715762

African (AFR) AF: 0.00 AC: 0 AN: 32870

American (AMR) AF: 0.00 AC: 0 AN: 41526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24698

East Asian (EAS) AF: 0.00 AC: 0 AN: 39530

South Asian (SAS) AF: 0.00 AC: 0 AN: 83988

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5660

European-Non Finnish (NFE) AF: 0.00000817 AC: 9 AN: 1101550

Other (OTH) AF: 0.0000168 AC: 1 AN: 59480

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.064
Eigen_PC	Benign	0.055
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		3.3
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.17
Sift	Benign	0.057	T
Sift4G	Benign	0.34	T
Polyphen		0.65	P
Vest4		0.83
MutPred		0.41		Gain of ubiquitination at T156 (P = 0.0031)
MVP		0.83
MPC		0.75
ClinPred		0.73	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.35
gMVP		0.57
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1030984404; hg19: chr19-13059361;