12-53502176-G-A

Position:

• chr12-53502176-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_134323.2(TARBP2):​c.215G>A​(p.Ser72Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TARBP2 NM_134323.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.47

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19457209).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TARBP2	NM_134323.2	c.215G>A	p.Ser72Asn	missense_variant	2/9	ENST00000266987.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TARBP2	ENST00000266987.7	c.215G>A	p.Ser72Asn	missense_variant	2/9	1	NM_134323.2	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 24, 2024

The c.215G>A (p.S72N) alteration is located in exon 2 (coding exon 2) of the TARBP2 gene. This alteration results from a G to A substitution at nucleotide position 215, causing the serine (S) at amino acid position 72 to be replaced by an asparagine (N). 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	0.25
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.25	T;.;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.79	T;.;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.69	N;.;.
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.88	N;N;N
REVEL	Benign	0.17
Sift	Benign	0.18	T;T;T
Sift4G	Benign	0.36	T;T;T
Polyphen		0.0020	B;.;.
Vest4		0.22
MutPred		0.33		Gain of catalytic residue at G77 (P = 0);.;.;
MVP		0.54
MPC		0.78
ClinPred		0.33	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.57

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

LitVar

Other links and lift over

dbSNP: rs1023348175; hg19: chr12-53895960;