NM_001114394.3:c.86T>C

Variant names:

• chr5-79619734-T-C
• NM_001114394.3:c.86T>C

Variant summary

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

The NM_001114394.3(TENT2):​c.86T>C​(p.Val29Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,604 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. 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: TENT2 NM_001114394.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.72

Genes affected

TENT2 (HGNC:26776): (terminal nucleotidyltransferase 2) Enables 5'-3' RNA polymerase activity and polynucleotide adenylyltransferase activity. Involved in RNA metabolic process and negative regulation of RNA catabolic process. Predicted to be located in nucleus. Predicted to be part of nuclear RNA-directed RNA polymerase complex. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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=0.14622629).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENT2	NM_001114394.3	c.86T>C	p.Val29Ala	missense_variant	Exon 2 of 15	ENST00000453514.6	NP_001107866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENT2	ENST00000453514.6	c.86T>C	p.Val29Ala	missense_variant	Exon 2 of 15	5	NM_001114394.3	ENSP00000397563.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461604 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727112

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.072	T;.;T;T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.096
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.72	T;T;T;.;.
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.15	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N;.;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.020	N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.093	T;T;T;T;T
Sift4G	Benign	0.20	T;T;T;T;T
Polyphen		0.025	B;B;B;B;B
Vest4		0.17
MutPred		0.51		Gain of disorder (P = 0.039);Gain of disorder (P = 0.039);Gain of disorder (P = 0.039);Gain of disorder (P = 0.039);Gain of disorder (P = 0.039);
MVP		0.46
MPC		0.26
ClinPred		0.41	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.065
gMVP		0.32

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: chr5-78915557; COSMIC: COSV57137641;