Variant 19-12948547-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005053.4(RAD23A):c.467C>T(p.Thr156Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000485 in 1,441,898 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

RAD23A
NM_005053.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.27

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]

RAD23A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RAD23A	NM_005053.4 linkuse as main transcript	c.467C>T	p.Thr156Met	missense_variant	4/9	ENST00000586534.6
RAD23A	NM_001270362.2 linkuse as main transcript	c.467C>T	p.Thr156Met	missense_variant	4/9
RAD23A	NM_001270363.2 linkuse as main transcript	c.467C>T	p.Thr156Met	missense_variant	4/8
RAD23A	NR_072976.2 linkuse as main transcript	n.504-139C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD23A	ENST00000586534.6 linkuse as main transcript	c.467C>T	p.Thr156Met	missense_variant	4/9	1	NM_005053.4	A1	P54725-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000426

AC:

AN:

234772

Hom.:

AF XY:

0.00000789

AC XY:

AN XY:

126822

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000938

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000485

AC:

AN:

1441898

Hom.:

Cov.:

AF XY:

0.00000559

AC XY:

AN XY:

715760

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:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000454

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.62

D;D;D

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.63

N;N;N

MutationTaster

Benign

0.89

D;D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.9

N;.;.

REVEL

Benign

0.10

Sift

Uncertain

0.022

D;.;.

Sift4G

Benign

0.061

T;T;D

Polyphen

0.27

.;B;.

Vest4

0.70

MutPred

0.35

Loss of glycosylation at S155 (P = 0.0251);Loss of glycosylation at S155 (P = 0.0251);Loss of glycosylation at S155 (P = 0.0251);

MVP

0.84

MPC

0.52

ClinPred

0.48

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.16

gMVP

0.44

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

Publications

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over