Genetic Variant TARBP2:p.Val90Glu (chr12-53503072-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_134323.2(TARBP2):c.269T>A(p.Val90Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000715 in 1,398,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

TARBP2
NM_134323.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00

Publications

0 publications found

Variant links:

Genes affected

TARBP2 (HGNC:11569): (TARBP2 subunit of RISC loading complex) 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. The protein encoded by this gene binds between the bulge and the loop of the HIV-1 TAR RNA regulatory element and activates HIV-1 gene expression in synergy with the viral Tat protein. Alternative splicing results in multiple transcript variants encoding different isoforms. This gene also has a pseudogene. [provided by RefSeq, Jul 2008]

TARBP2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19502512).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_134323.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TARBP2	NM_134323.2	MANE Select	c.269T>A	p.Val90Glu	missense	Exon 3 of 9	NP_599150.1	Q15633-1
TARBP2	NM_004178.5		c.206T>A	p.Val69Glu	missense	Exon 3 of 9	NP_004169.3
TARBP2	NM_134324.3		c.206T>A	p.Val69Glu	missense	Exon 3 of 9	NP_599151.2	Q15633-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TARBP2	ENST00000266987.7	TSL:1 MANE Select	c.269T>A	p.Val90Glu	missense	Exon 3 of 9	ENSP00000266987.2	Q15633-1
TARBP2	ENST00000456234.6	TSL:1	c.206T>A	p.Val69Glu	missense	Exon 3 of 9	ENSP00000416077.2	Q15633-2
TARBP2	ENST00000549610.5	TSL:1	n.376T>A		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1398624

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689874

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31542

American (AMR)

AF:

0.00

AC:

AN:

35672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25152

East Asian (EAS)

AF:

0.00

AC:

AN:

35618

South Asian (SAS)

AF:

0.00

AC:

AN:

79102

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49320

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078586

Other (OTH)

AF:

0.00

AC:

AN:

57954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Uncertain

0.040

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.17

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.43

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.78

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.56

PhyloP100

4.0

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.87

REVEL

Uncertain

0.34

Sift

Benign

0.042

Sift4G

Uncertain

0.037

Polyphen

0.46

Vest4

0.46

MutPred

0.51

Loss of MoRF binding (P = 0.0219)

MVP

0.63

MPC

2.3

ClinPred

0.84

GERP RS

1.8

Varity_R

0.29

gMVP

0.72

Mutation Taster

=61/39

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over