5-79642871-A-C

Position:

• chr5-79642871-A-C

Variant summary

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

The NM_001114394.3(TENT2):​c.712A>C​(p.Ile238Leu) 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. 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: 4.78

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=0.15914473).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENT2	NM_001114394.3	c.712A>C	p.Ile238Leu	missense_variant	7/15	ENST00000453514.6	NP_001107866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TENT2	ENST00000453514.6	c.712A>C	p.Ile238Leu	missense_variant	7/15	5	NM_001114394.3	ENSP00000397563	A1
TENT2	ENST00000423041.6	c.700A>C	p.Ile234Leu	missense_variant	8/16	1		ENSP00000393412	P4
TENT2	ENST00000504233.5	c.712A>C	p.Ile238Leu	missense_variant	7/14	1		ENSP00000421966
TENT2	ENST00000296783.7	c.712A>C	p.Ile238Leu	missense_variant	8/16	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

Jun 09, 2022

The c.712A>C (p.I238L) alteration is located in exon 7 (coding exon 6) of the PAPD4 gene. This alteration results from a A to C substitution at nucleotide position 712, causing the isoleucine (I) at amino acid position 238 to be replaced by a leucine (L). 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	0.41
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T;.;T;T;T
Eigen	Benign	-0.031
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D;D;T;.;.
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.16	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.91	L;.;.;L;L
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.82	N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.54	T;T;T;T;T
Sift4G	Benign	0.63	T;T;T;T;T
Polyphen		0.23	B;B;P;B;B
Vest4		0.47
MutPred		0.49		Loss of MoRF binding (P = 0.1624);.;Loss of MoRF binding (P = 0.1624);Loss of MoRF binding (P = 0.1624);Loss of MoRF binding (P = 0.1624);
MVP		0.40
MPC		0.29
ClinPred		0.50	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr5-78938694; COSMIC: COSV57136196; COSMIC: COSV57136196;