1-234391666-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_005646.4(TARBP1):​c.4777C>T​(p.Arg1593Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,613,672 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 (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

TARBP1
NM_005646.4 missense

Scores

12
4
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.96

Publications

1 publications found
Variant links:
Genes affected
TARBP1 (HGNC:11568): (TAR (HIV-1) RNA binding protein 1) HIV-1, the causative agent of acquired immunodeficiency syndrome (AIDS), contains an RNA genome that produces a chromosomally integrated DNA during the replicative cycle. Activation of HIV-1 gene expression by the transactivator Tat is dependent on an RNA regulatory element (TAR) located downstream of the transcription initiation site. This element forms a stable stem-loop structure and can be bound by either the protein encoded by this gene or by RNA polymerase II. This protein may act to disengage RNA polymerase II from TAR during transcriptional elongation. Alternatively spliced transcripts of this gene may exist, but their full-length natures have not been determined. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.813

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TARBP1NM_005646.4 linkc.4777C>T p.Arg1593Cys missense_variant Exon 30 of 30 ENST00000040877.2 NP_005637.3 Q13395

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TARBP1ENST00000040877.2 linkc.4777C>T p.Arg1593Cys missense_variant Exon 30 of 30 1 NM_005646.4 ENSP00000040877.1 Q13395

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152136
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000876
AC:
22
AN:
251216
AF XY:
0.0000957
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000435
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000438
AC:
64
AN:
1461418
Hom.:
0
Cov.:
31
AF XY:
0.0000536
AC XY:
39
AN XY:
727006
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33468
American (AMR)
AF:
0.00
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.0000383
AC:
1
AN:
26128
East Asian (EAS)
AF:
0.000126
AC:
5
AN:
39700
South Asian (SAS)
AF:
0.000220
AC:
19
AN:
86170
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53406
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5486
European-Non Finnish (NFE)
AF:
0.0000324
AC:
36
AN:
1111974
Other (OTH)
AF:
0.0000497
AC:
3
AN:
60366
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.442
Heterozygous variant carriers
0
4
7
11
14
18
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152254
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74448
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41532
American (AMR)
AF:
0.00
AC:
0
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.000193
AC:
1
AN:
5184
South Asian (SAS)
AF:
0.000414
AC:
2
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10598
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68028
Other (OTH)
AF:
0.00
AC:
0
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0000503
Hom.:
0
Bravo
AF:
0.0000227
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.000519
AC:
2
ExAC
AF:
0.0000906
AC:
11
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 06, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.4777C>T (p.R1593C) alteration is located in exon 30 (coding exon 30) of the TARBP1 gene. This alteration results from a C to T substitution at nucleotide position 4777, causing the arginine (R) at amino acid position 1593 to be replaced by a cysteine (C). 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
0.60
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Uncertain
-0.060
CADD
Pathogenic
34
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.40
T
Eigen
Pathogenic
0.98
Eigen_PC
Pathogenic
0.89
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Uncertain
0.088
D
MetaRNN
Pathogenic
0.81
D
MetaSVM
Uncertain
-0.12
T
MutationAssessor
Pathogenic
3.5
H
PhyloP100
10
PrimateAI
Uncertain
0.76
T
PROVEAN
Pathogenic
-6.6
D
REVEL
Pathogenic
0.69
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.88
MVP
0.67
MPC
0.31
ClinPred
0.90
D
GERP RS
5.5
Varity_R
0.89
gMVP
0.79
Mutation Taster
=19/81
disease causing

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

Other links and lift over

dbSNP: rs560732693; hg19: chr1-234527412; API