Variant chr5-79648619-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001114394.3(TENT2):c.824G>T(p.Cys275Phe) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000707 in 1,414,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

TENT2
NM_001114394.3 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.56

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=0.26417577).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENT2	NM_001114394.3 linkuse as main transcript	c.824G>T	p.Cys275Phe	missense_variant, splice_region_variant	9/15	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.824G>T	p.Cys275Phe	missense_variant, splice_region_variant	9/15	5	NM_001114394.3	ENSP00000397563	A1	Q6PIY7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.07e-7

AC:

AN:

1414550

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

704404

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

Cov.:

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 07, 2023

The c.824G>T (p.C275F) alteration is located in exon 9 (coding exon 8) of the PAPD4 gene. This alteration results from a G to T substitution at nucleotide position 824, causing the cysteine (C) at amino acid position 275 to be replaced by a phenylalanine (F). 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

0.18

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

T;.;T;T;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.83

T;T;T;.;.

M_CAP

Benign

0.021

MetaRNN

Benign

0.26

T;T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.7

L;.;.;L;L

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.95

N;N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.035

D;D;D;D;D

Sift4G

Uncertain

0.037

D;D;D;D;D

Polyphen

0.039

B;B;D;B;B

Vest4

0.31

MutPred

0.64

Gain of sheet (P = 0.0827);.;Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.64

MPC

0.33

ClinPred

0.76

GERP RS

6.0

Varity_R

0.27

gMVP

0.33

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over