rs778306837

Variant names:

• chr19-12949145-C-G
• rs778306837
• NM_005053.4:c.665C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-12949145-C-G
• chr19-12949145-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005053.4(RAD23A):​c.665C>G​(p.Pro222Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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. P222L) 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: 3.59

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1206823).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD23A	NM_005053.4	c.665C>G	p.Pro222Arg	missense_variant	Exon 6 of 9	ENST00000586534.6	NP_005044.1
RAD23A	NM_001270362.2	c.665C>G	p.Pro222Arg	missense_variant	Exon 6 of 9		NP_001257291.1
RAD23A	NM_001270363.2	c.665C>G	p.Pro222Arg	missense_variant	Exon 6 of 8		NP_001257292.1
RAD23A	NR_072976.2	n.696C>G		non_coding_transcript_exon_variant	Exon 5 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD23A	ENST00000586534.6	c.665C>G	p.Pro222Arg	missense_variant	Exon 6 of 9	1	NM_005053.4	ENSP00000467024.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000800 AC: 2 AN: 250126 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135298

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	.;T;.;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.82	T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N;N;.
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.6	D;.;.;.
REVEL	Benign	0.066
Sift	Benign	0.062	T;.;.;.
Sift4G	Benign	0.12	T;T;T;T
Polyphen		0.0070	.;B;.;.
Vest4		0.54
MutPred		0.14		Loss of glycosylation at S219 (P = 0.1191);Loss of glycosylation at S219 (P = 0.1191);Loss of glycosylation at S219 (P = 0.1191);.;
MVP		0.67
MPC		0.45
ClinPred		0.24	T
GERP RS		3.5
Varity_R		0.12
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs778306837; hg19: chr19-13059959;