Variant 5-79649137-G-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.974G>A(p.Arg325His) variant causes a missense change. The variant allele was found at a frequency of 0.000397 in 1,613,488 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 0 hom. )

Consequence

TENT2
NM_001114394.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.41

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=0.11435169).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENT2	NM_001114394.3 linkuse as main transcript	c.974G>A	p.Arg325His	missense_variant	10/15	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.974G>A	p.Arg325His	missense_variant	10/15	5	NM_001114394.3	ENSP00000397563	A1	Q6PIY7-1

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000251

AC:

AN:

250840

Hom.:

AF XY:

0.000280

AC XY:

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000344

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000407

AC:

594

AN:

1461216

Hom.:

Cov.:

AF XY:

0.000384

AC XY:

279

AN XY:

726890

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.000689

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000244

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000469

Gnomad4 OTH exome

AF:

0.000364

GnomAD4 genome

AF:

0.000302

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000411

Hom.:

Bravo

AF:

0.000302

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000264

AC:

EpiCase

AF:

0.000764

EpiControl

AF:

0.000237

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

Feb 16, 2023

The c.974G>A (p.R325H) alteration is located in exon 10 (coding exon 9) of the PAPD4 gene. This alteration results from a G to A substitution at nucleotide position 974, causing the arginine (R) at amino acid position 325 to be replaced by a histidine (H). 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

0.15

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

T;.;T;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

D;D;.;.

M_CAP

Benign

0.027

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.1

M;.;M;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-2.2

N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.10

T;T;T;T

Sift4G

Benign

0.17

T;T;T;T

Polyphen

0.69

P;P;P;P

Vest4

0.41

MVP

0.67

MPC

0.88

ClinPred

0.079

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.41

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

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