NM_001114394.3:c.648A>T

Variant names:

• chr5-79641172-A-T
• NM_001114394.3:c.648A>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114394.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENT2	NM_001114394.3	MANE Select	c.648A>T	p.Leu216Phe	missense	Exon 6 of 15	NP_001107866.1	Q6PIY7-1
	TENT2	NM_001349548.2		c.-73A>T		5_prime_UTR_premature_start_codon_gain	Exon 7 of 17	NP_001336477.1
	TENT2	NM_001349549.2		c.648A>T	p.Leu216Phe	missense	Exon 6 of 15	NP_001336478.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENT2	ENST00000453514.6	TSL:5 MANE Select	c.648A>T	p.Leu216Phe	missense	Exon 6 of 15	ENSP00000397563.1	Q6PIY7-1
	TENT2	ENST00000423041.6	TSL:1	c.648A>T	p.Leu216Phe	missense	Exon 7 of 16	ENSP00000393412.2	Q6PIY7-2
	TENT2	ENST00000504233.5	TSL:1	c.648A>T	p.Leu216Phe	missense	Exon 6 of 14	ENSP00000421966.1	D6RAF2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.2
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.012	D
Sift4G	Benign	0.10	T
Polyphen		0.78	P
Vest4		0.62
MutPred		0.36		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
Mutation Taster		=10/90	disease causing

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

Other links and lift over

hg19: chr5-78936995;