chr5-79641172-A-T

Position:

• chr5-79641172-A-T

Variant summary

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

The NM_001114394.3(TENT2):​c.648A>T​(p.Leu216Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TENT2 NM_001114394.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENT2	NM_001114394.3	c.648A>T	p.Leu216Phe	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	c.648A>T	p.Leu216Phe	missense_variant	6/15	5	NM_001114394.3	ENSP00000397563	A1
TENT2	ENST00000423041.6	c.648A>T	p.Leu216Phe	missense_variant	7/16	1		ENSP00000393412	P4
TENT2	ENST00000504233.5	c.648A>T	p.Leu216Phe	missense_variant	6/14	1		ENSP00000421966
TENT2	ENST00000296783.7	c.648A>T	p.Leu216Phe	missense_variant	7/16	2		ENSP00000296783	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 29, 2024

The c.648A>T (p.L216F) alteration is located in exon 6 (coding exon 5) of the PAPD4 gene. This alteration results from a A to T substitution at nucleotide position 648, causing the leucine (L) at amino acid position 216 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	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D;.;T;D;D
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.95	D;D;D;.;.
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.58	D;D;D;D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.4	M;M;.;M;M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.6	D;D;D;D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.012	D;D;D;D;D
Sift4G	Benign	0.10	T;D;D;T;T
Polyphen		0.78	P;P;D;P;P
Vest4		0.62
MutPred		0.36		Gain of catalytic residue at L216 (P = 0.0736);Gain of catalytic residue at L216 (P = 0.0736);Gain of catalytic residue at L216 (P = 0.0736);Gain of catalytic residue at L216 (P = 0.0736);Gain of catalytic residue at L216 (P = 0.0736);
MVP		0.69
MPC		0.61
ClinPred		0.92	D
GERP RS		3.5
Varity_R		0.26
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr5-78936995;