16-50153908-T-A

Variant names:

• chr16-50153908-T-A
• NM_001365324.3:c.287T>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001365324.3(TENT4B):​c.287T>A​(p.Leu96Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/18 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)
• Consequence: TENT4B NM_001365324.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.145

Genes affected

TENT4B (HGNC:30758): (terminal nucleotidyltransferase 4B) Enables guanylyltransferase activity and polynucleotide adenylyltransferase activity. Involved in several processes, including RNA metabolic process; negative regulation of telomere maintenance via telomerase; and regulation of mRNA stability. Located in cytoplasm and nucleolus. Part of TRAMP complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047532886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENT4B	NM_001365324.3	c.287T>A	p.Leu96Gln	missense_variant	Exon 1 of 12	ENST00000561678.7	NP_001352253.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENT4B	ENST00000561678.7	c.287T>A	p.Leu96Gln	missense_variant	Exon 1 of 12	5	NM_001365324.3	ENSP00000455837.3
TENT4B	ENST00000436909.8	c.242T>A	p.Leu81Gln	missense_variant	Exon 2 of 13	2		ENSP00000396995.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.242T>A (p.L81Q) alteration is located in exon 2 (coding exon 2) of the PAPD5 gene. This alteration results from a T to A substitution at nucleotide position 242, causing the leucine (L) at amino acid position 81 to be replaced by a glutamine (Q). 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
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Uncertain	0.97
DEOGEN2	Benign	0.011	.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.048	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.39	N;N
REVEL	Benign	0.064
Sift	Benign	0.075	T;T
Sift4G	Benign	0.60	T;D
Vest4		0.085
MVP		0.13
MPC		1.3
ClinPred		0.053	T
GERP RS		-6.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.11

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: chr16-50187819;