Variant 12-53503072-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 made for transcript

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=0.19502512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TARBP2	NM_134323.2 link	c.269T>A	p.Val90Glu	missense_variant	Exon 3 of 9	ENST00000266987.7	NP_599150.1	Q15633-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TARBP2	ENST00000266987.7 link	c.269T>A	p.Val90Glu	missense_variant	Exon 3 of 9	1	NM_134323.2	ENSP00000266987.2		Q15633-1

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

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.27e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.269T>A (p.V90E) alteration is located in exon 3 (coding exon 3) of the TARBP2 gene. This alteration results from a T to A substitution at nucleotide position 269, causing the valine (V) at amino acid position 90 to be replaced by a glutamic acid (E). 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

Benign

0.27

BayesDel_addAF

Uncertain

0.040

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.17

T;.;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.43

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.78

T;.;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.56

N;.;.

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.87

N;N;N

REVEL

Uncertain

0.34

Sift

Benign

0.042

D;D;D

Sift4G

Uncertain

0.037

D;D;D

Polyphen

0.46

P;.;.

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

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over