19-12948730-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_005053.4(RAD23A):ā€‹c.517A>Gā€‹(p.Met173Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

RAD23A
NM_005053.4 missense

Scores

5
12
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.86
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.885

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RAD23ANM_005053.4 linkuse as main transcriptc.517A>G p.Met173Val missense_variant 5/9 ENST00000586534.6
RAD23ANM_001270362.2 linkuse as main transcriptc.517A>G p.Met173Val missense_variant 5/9
RAD23ANM_001270363.2 linkuse as main transcriptc.517A>G p.Met173Val missense_variant 5/8
RAD23ANR_072976.2 linkuse as main transcriptn.548A>G non_coding_transcript_exon_variant 4/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RAD23AENST00000586534.6 linkuse as main transcriptc.517A>G p.Met173Val missense_variant 5/91 NM_005053.4 A1P54725-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250818
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135586
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461352
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727016
show subpopulations
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 27, 2024The c.517A>G (p.M173V) alteration is located in exon 5 (coding exon 5) of the RAD23A gene. This alteration results from a A to G substitution at nucleotide position 517, causing the methionine (M) at amino acid position 173 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.81
BayesDel_addAF
Uncertain
0.16
D
BayesDel_noAF
Uncertain
0.080
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.45
.;T;.
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.92
D;D;D
M_CAP
Benign
0.064
D
MetaRNN
Pathogenic
0.88
D;D;D
MetaSVM
Uncertain
0.062
D
MutationAssessor
Pathogenic
4.2
H;H;H
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.60
T
PROVEAN
Uncertain
-3.8
D;.;.
REVEL
Uncertain
0.55
Sift
Uncertain
0.0020
D;.;.
Sift4G
Uncertain
0.0030
D;D;D
Polyphen
0.71
.;P;.
Vest4
0.65
MutPred
0.89
Loss of disorder (P = 0.0825);Loss of disorder (P = 0.0825);Loss of disorder (P = 0.0825);
MVP
0.86
MPC
1.1
ClinPred
0.99
D
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.87
gMVP
0.96

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1314975685; hg19: chr19-13059544; API