Variant 5-79656999-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001114394.3(TENT2):c.1069C>A(p.Pro357Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000712 in 1,586,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

TENT2
NM_001114394.3 missense, splice_region

Scores

Splicing: ADA: 0.9479

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.22

Variant links:

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]

TENT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.120901704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENT2	NM_001114394.3 linkuse as main transcript	c.1069C>A	p.Pro357Thr	missense_variant, splice_region_variant	11/15	ENST00000453514.6	NP_001107866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TENT2	ENST00000453514.6 linkuse as main transcript	c.1069C>A	p.Pro357Thr	missense_variant, splice_region_variant	11/15	5	NM_001114394.3	ENSP00000397563	A1	Q6PIY7-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

151838

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000164

AC:

AN:

249350

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

135018

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00329

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000443

Gnomad OTH exome

AF:

0.000495

GnomAD4 exome

AF:

0.0000676

AC:

AN:

1434684

Hom.:

Cov.:

AF XY:

0.0000755

AC XY:

AN XY:

715086

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00301

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000826

Gnomad4 OTH exome

AF:

0.000168

GnomAD4 genome

AF:

0.000105

AC:

AN:

151838

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

74146

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00433

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000251

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000157

AC:

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

Nov 06, 2023

The c.1069C>A (p.P357T) alteration is located in exon 11 (coding exon 10) of the PAPD4 gene. This alteration results from a C to A substitution at nucleotide position 1069, causing the proline (P) at amino acid position 357 to be replaced by a threonine (T). 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

Uncertain

0.35

BayesDel_addAF

Uncertain

0.033

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.64

D;.;T;D;D

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.78

T;T;T;.;.

M_CAP

Benign

0.079

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Uncertain

-0.20

MutationAssessor

Uncertain

2.9

M;.;.;M;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-6.0

D;D;D;D;D

REVEL

Uncertain

0.45

Sift

Uncertain

0.011

D;D;D;D;D

Sift4G

Uncertain

0.026

D;D;D;D;D

Polyphen

0.95

P;D;D;P;P

Vest4

0.73

MVP

0.86

MPC

0.86

ClinPred

0.49

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.55

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.95

dbscSNV1_RF

Pathogenic

0.78

SpliceAI score (max)

0.090

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over