Genetic Variant TENT2:p.Arg236Trp (chr5-79642865-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001114394.3(TENT2):c.706C>T(p.Arg236Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000493 in 1,459,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

TENT2
NM_001114394.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.19

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39436293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENT2	NM_001114394.3 link	c.706C>T	p.Arg236Trp	missense_variant	Exon 7 of 15	ENST00000453514.6	NP_001107866.1	Q6PIY7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TENT2	ENST00000453514.6 link	c.706C>T	p.Arg236Trp	missense_variant	Exon 7 of 15	5	NM_001114394.3	ENSP00000397563.1	Q6PIY7-1
TENT2	ENST00000423041.6 link	c.694C>T	p.Arg232Trp	missense_variant	Exon 8 of 16	1		ENSP00000393412.2	Q6PIY7-2
TENT2	ENST00000504233.5 link	c.706C>T	p.Arg236Trp	missense_variant	Exon 7 of 14	1		ENSP00000421966.1	D6RAF2
TENT2	ENST00000296783.7 link	c.706C>T	p.Arg236Trp	missense_variant	Exon 8 of 16	2		ENSP00000296783.3	Q6PIY7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000320

AC:

AN:

250002

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000493

AC:

AN:

1459336

Hom.:

Cov.:

AF XY:

0.0000565

AC XY:

AN XY:

726006

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000163

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000513

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.706C>T (p.R236W) alteration is located in exon 7 (coding exon 6) of the PAPD4 gene. This alteration results from a C to T substitution at nucleotide position 706, causing the arginine (R) at amino acid position 236 to be replaced by a tryptophan (W). 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

0.52

BayesDel_addAF

Benign

-0.0028

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

T;.;T;T;T

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.94

D;D;D;.;.

M_CAP

Benign

0.018

MetaRNN

Benign

0.39

T;T;T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.1

M;.;.;M;M

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.3

N;N;N;N;N

REVEL

Benign

0.26

Sift

Uncertain

0.011

D;D;D;D;D

Sift4G

Uncertain

0.031

D;T;D;D;D

Polyphen

0.99

D;P;D;D;D

Vest4

0.57

MutPred

0.51

Loss of helix (P = 0.0444);.;Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);

MVP

0.56

MPC

0.78

ClinPred

0.57

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.092

gMVP

0.60

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