chr12-53503101-A-G

Variant names:

• chr12-53503101-A-G
• rs1289122609
• NM_134323.2:c.298A>G

Variant summary

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

The NM_134323.2(TARBP2):​c.298A>G​(p.Met100Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,398,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TARBP2 NM_134323.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.61

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=0.2535184).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TARBP2	NM_134323.2	c.298A>G	p.Met100Val	missense_variant	Exon 3 of 9	ENST00000266987.7	NP_599150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TARBP2	ENST00000266987.7	c.298A>G	p.Met100Val	missense_variant	Exon 3 of 9	1	NM_134323.2	ENSP00000266987.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000129 AC: 2 AN: 155078 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 81684

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000180

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398256 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 689734

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000562

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.298A>G (p.M100V) alteration is located in exon 3 (coding exon 3) of the TARBP2 gene. This alteration results from a A to G substitution at nucleotide position 298, causing the methionine (M) at amino acid position 100 to be replaced by a valine (V). 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	0.085
BayesDel_addAF	Benign	-0.00092	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.086	T;.;.;T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.094
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.73	T;.;D;D;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	N;.;.;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.23	N;N;D;N;N
REVEL	Benign	0.051
Sift	Benign	0.36	T;T;.;D;T
Sift4G	Benign	0.62	T;T;D;D;T
Polyphen		0.077	B;.;.;.;.
Vest4		0.31
MVP		0.53
MPC		0.79
ClinPred		0.14	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.53

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: rs1289122609; hg19: chr12-53896885;