12-53504717-G-A

Variant names:

• chr12-53504717-G-A
• NM_134323.2:c.515G>A

Variant summary

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

The NM_134323.2(TARBP2):​c.515G>A​(p.Gly172Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TARBP2 NM_134323.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.41

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]

ACMG classification

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 rank	MANE	Protein	UniProt
TARBP2	NM_134323.2	c.515G>A	p.Gly172Asp	missense_variant	Exon 6 of 9	ENST00000266987.7	NP_599150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TARBP2	ENST00000266987.7	c.515G>A	p.Gly172Asp	missense_variant	Exon 6 of 9	1	NM_134323.2	ENSP00000266987.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727242

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	32
DANN	Benign	0.89
DEOGEN2	Uncertain	0.58	D;.;.;.;T;.
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;.;D;D;D;D
M_CAP	Pathogenic	0.31	D
MetaRNN	Uncertain	0.73	D;D;D;D;D;D
MetaSVM	Uncertain	0.20	D
MutationAssessor	Uncertain	2.6	M;.;.;.;.;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.6	D;D;D;.;D;D
REVEL	Pathogenic	0.68
Sift	Uncertain	0.0090	D;D;D;.;T;D
Sift4G	Uncertain	0.020	D;D;D;D;D;D
Polyphen		1.0	D;.;.;.;.;.
Vest4		0.69
MutPred		0.45		Gain of catalytic residue at P176 (P = 0.0055);.;.;.;.;.;
MVP		0.96
MPC		2.1
ClinPred		0.91	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.86
gMVP		0.71

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.

Other links and lift over

hg19: chr12-53898501;