chr16-50154194-C-G

Position:

• chr16-50154194-C-G

Variant summary

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

The NM_001365324.3(TENT4B):​c.573C>G​(p.Asp191Glu) 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. 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: 1.97

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]

TENT4B (HGNC:):

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=0.08606595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENT4B	NM_001365324.3	c.573C>G	p.Asp191Glu	missense_variant	1/12	ENST00000561678.7	NP_001352253.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TENT4B	ENST00000561678.7	c.573C>G	p.Asp191Glu	missense_variant	1/12	5	NM_001365324.3	ENSP00000455837.3
TENT4B	ENST00000436909.8	c.528C>G	p.Asp176Glu	missense_variant	2/13	2		ENSP00000396995.3
TENT4B	ENST00000562717.1	n.34C>G		non_coding_transcript_exon_variant	1/13	5

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.528C>G (p.D176E) alteration is located in exon 2 (coding exon 2) of the PAPD5 gene. This alteration results from a C to G substitution at nucleotide position 528, causing the aspartic acid (D) at amino acid position 176 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
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0059	.;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.51	T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.086	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.60	D;N;N
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.19	N;N
REVEL	Benign	0.087
Sift	Benign	0.31	T;T
Sift4G	Benign	1.0	T;T
Vest4		0.045
MVP		0.22
MPC		1.2
ClinPred		0.12	T
GERP RS		2.9
gMVP		0.28

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: chr16-50188105;