19-12949151-CG-GA

Variant names:

• chr19-12949151-CG-GA
• NM_005053.4:c.671_672delCGinsGA
• RAD23A p.Thr224Arg

Variant summary

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

The NM_005053.4(RAD23A):​c.671_672delCGinsGA​(p.Thr224Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. T224M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAD23A NM_005053.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• 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 0 ACMG points.

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.671_672delCGinsGA	p.Thr224Arg	missense	N/A	NP_005044.1	P54725-1
	RAD23A	NM_001270362.2		c.671_672delCGinsGA	p.Thr224Arg	missense	N/A	NP_001257291.1	P54725-3
	RAD23A	NM_001270363.2		c.671_672delCGinsGA	p.Thr224Arg	missense	N/A	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.671_672delCGinsGA	p.Thr224Arg	missense	N/A	ENSP00000467024.1	P54725-1
	RAD23A	ENST00000316856.7	TSL:1	c.671_672delCGinsGA	p.Thr224Arg	missense	N/A	ENSP00000321365.3	P54725-3
	RAD23A	ENST00000875551.1		c.665_666delCGinsGA	p.Thr222Arg	missense	N/A	ENSP00000545610.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-13059965;