Variant 5-79640934-G-C 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.549G>C(p.Gln183His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TENT2
NM_001114394.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.447

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.075669974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENT2	NM_001114394.3 link	c.549G>C	p.Gln183His	missense_variant	5/15	ENST00000453514.6	NP_001107866.1	Q6PIY7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TENT2	ENST00000453514.6 link	c.549G>C	p.Gln183His	missense_variant	5/15	5	NM_001114394.3	ENSP00000397563.1	Q6PIY7-1
TENT2	ENST00000423041.6 link	c.549G>C	p.Gln183His	missense_variant	6/16	1		ENSP00000393412.2	Q6PIY7-2
TENT2	ENST00000504233.5 link	c.549G>C	p.Gln183His	missense_variant	5/14	1		ENSP00000421966.1	D6RAF2
TENT2	ENST00000296783.7 link	c.549G>C	p.Gln183His	missense_variant	6/16	2		ENSP00000296783.3	Q6PIY7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458324

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725398

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:

0.0000351

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

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

Aug 05, 2024

The c.549G>C (p.Q183H) alteration is located in exon 5 (coding exon 4) of the PAPD4 gene. This alteration results from a G to C substitution at nucleotide position 549, causing the glutamine (Q) at amino acid position 183 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

0.28

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.085

T;.;T;T;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.46

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.83

T;T;T;.;.

M_CAP

Benign

0.014

MetaRNN

Benign

0.076

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.64

N;N;.;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

0.20

N;N;N;N;N

REVEL

Benign

0.011

Sift

Benign

0.48

T;T;T;T;T

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

0.0

B;B;B;B;B

Vest4

0.32

MutPred

0.39

Loss of disorder (P = 0.0477);Loss of disorder (P = 0.0477);Loss of disorder (P = 0.0477);Loss of disorder (P = 0.0477);Loss of disorder (P = 0.0477);

MVP

0.28

MPC

0.27

ClinPred

0.072

GERP RS

1.2

Varity_R

0.032

gMVP

0.37

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