5-79642850-C-G

Variant names:

• chr5-79642850-C-G
• NM_001114394.3:c.691C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001114394.3(TENT2):​c.691C>G​(p.Gln231Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TENT2 NM_001114394.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.43

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]

ACMG classification

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=0.2271631).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENT2	NM_001114394.3	c.691C>G	p.Gln231Glu	missense_variant	Exon 7 of 15	ENST00000453514.6	NP_001107866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENT2	ENST00000453514.6	c.691C>G	p.Gln231Glu	missense_variant	Exon 7 of 15	5	NM_001114394.3	ENSP00000397563.1
TENT2	ENST00000423041.6	c.679C>G	p.Gln227Glu	missense_variant	Exon 8 of 16	1		ENSP00000393412.2
TENT2	ENST00000504233.5	c.691C>G	p.Gln231Glu	missense_variant	Exon 7 of 14	1		ENSP00000421966.1
TENT2	ENST00000296783.7	c.691C>G	p.Gln231Glu	missense_variant	Exon 8 of 16	2		ENSP00000296783.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1458516 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725658

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: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.691C>G (p.Q231E) alteration is located in exon 7 (coding exon 6) of the PAPD4 gene. This alteration results from a C to G substitution at nucleotide position 691, causing the glutamine (Q) at amino acid position 231 to be replaced by a glutamic acid (E). 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	0.48
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T;.;T;T;T
Eigen	Benign	0.038
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.82	T;D;T;.;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.23	T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L;.;.;L;L
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.4	N;N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.050	D;T;D;D;D
Sift4G	Benign	0.079	T;D;T;T;T
Polyphen		0.15	B;B;P;B;B
Vest4		0.47
MutPred		0.40		Gain of helix (P = 0.062);.;Gain of helix (P = 0.062);Gain of helix (P = 0.062);Gain of helix (P = 0.062);
MVP		0.64
MPC		0.47
ClinPred		0.67	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.44

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.

Other links and lift over

hg19: chr5-78938673;