Variant 1-234393807-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005646.4(TARBP1):c.4274C>G(p.Ala1425Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1425V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TARBP1
NM_005646.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.52

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]

TARBP1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055767268).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TARBP1	NM_005646.4 linkuse as main transcript	c.4274C>G	p.Ala1425Gly	missense_variant	27/30	ENST00000040877.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TARBP1	ENST00000040877.2 linkuse as main transcript	c.4274C>G	p.Ala1425Gly	missense_variant	27/30	1	NM_005646.4	P1
TARBP1	ENST00000462259.5 linkuse as main transcript	n.859C>G		non_coding_transcript_exon_variant	5/8	1
TARBP1	ENST00000483404.5 linkuse as main transcript	n.2262C>G		non_coding_transcript_exon_variant	4/7	2
TARBP1	ENST00000496673.5 linkuse as main transcript	n.239C>G		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460644

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726500

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:

9.00e-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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2022

The c.4274C>G (p.A1425G) alteration is located in exon 27 (coding exon 27) of the TARBP1 gene. This alteration results from a C to G substitution at nucleotide position 4274, causing the alanine (A) at amino acid position 1425 to be replaced by a glycine (G). 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

0.082

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.0076

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.73

M_CAP

Benign

0.0064

MetaRNN

Benign

0.056

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

0.15

REVEL

Benign

0.031

Sift

Benign

0.40

Sift4G

Benign

0.19

Polyphen

0.033

Vest4

0.12

MutPred

0.37

Loss of sheet (P = 0.003);

MVP

0.095

MPC

0.044

ClinPred

0.15

GERP RS

2.6

Varity_R

0.028

gMVP

0.37

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