Variant chr5-79641149-A-G 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.625A>G(p.Thr209Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000101 in 1,579,360 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000086 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

TENT2
NM_001114394.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.57

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=0.08527744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENT2	NM_001114394.3 linkuse as main transcript	c.625A>G	p.Thr209Ala	missense_variant	6/15	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.625A>G	p.Thr209Ala	missense_variant	6/15	5	NM_001114394.3	ENSP00000397563	A1	Q6PIY7-1
TENT2	ENST00000423041.6 linkuse as main transcript	c.625A>G	p.Thr209Ala	missense_variant	7/16	1		ENSP00000393412	P4	Q6PIY7-2
TENT2	ENST00000504233.5 linkuse as main transcript	c.625A>G	p.Thr209Ala	missense_variant	6/14	1		ENSP00000421966
TENT2	ENST00000296783.7 linkuse as main transcript	c.625A>G	p.Thr209Ala	missense_variant	7/16	2		ENSP00000296783	A1	Q6PIY7-1

Frequencies

GnomAD3 genomes

AF:

0.0000856

AC:

AN:

151790

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000136

AC:

AN:

219992

Hom.:

AF XY:

0.000208

AC XY:

AN XY:

120084

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000207

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000239

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000102

AC:

146

AN:

1427452

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

709962

show subpopulations

Gnomad4 AFR exome

AF:

0.0000323

Gnomad4 AMR exome

AF:

0.000296

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000227

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000925

Gnomad4 OTH exome

AF:

0.000119

GnomAD4 genome

AF:

0.0000856

AC:

AN:

151908

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000624

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.000112

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.000148

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

May 24, 2024

The c.625A>G (p.T209A) alteration is located in exon 6 (coding exon 5) of the PAPD4 gene. This alteration results from a A to G substitution at nucleotide position 625, causing the threonine (T) at amino acid position 209 to be replaced by an alanine (A). 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

0.14

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.26

T;.;T;T;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.74

T;T;T;.;.

M_CAP

Benign

0.0092

MetaRNN

Benign

0.085

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L;.;L;L

MutationTaster

Benign

0.97

D;D;D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.1

N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.20

T;T;T;T;T

Sift4G

Benign

0.15

T;T;T;T;T

Polyphen

0.0

B;B;B;B;B

Vest4

0.22

MutPred

0.30

Loss of disorder (P = 0.1716);Loss of disorder (P = 0.1716);Loss of disorder (P = 0.1716);Loss of disorder (P = 0.1716);Loss of disorder (P = 0.1716);

MVP

0.37

MPC

0.21

ClinPred

0.098

GERP RS

1.7

Varity_R

0.052

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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