Genetic Variant TENT4B:p.Asn112Ser (chr16-50153956-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001365324.3(TENT4B):c.335A>G(p.Asn112Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000032 in 1,533,228 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

TENT4B
NM_001365324.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.05

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06921145).

BS2

High AC in GnomAdExome4 at 48 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENT4B	NM_001365324.3 link	c.335A>G	p.Asn112Ser	missense_variant	Exon 1 of 12	ENST00000561678.7	NP_001352253.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TENT4B	ENST00000561678.7 link	c.335A>G	p.Asn112Ser	missense_variant	Exon 1 of 12	5	NM_001365324.3	ENSP00000455837.3	A0A7N4YH79
TENT4B	ENST00000436909.8 link	c.290A>G	p.Asn97Ser	missense_variant	Exon 2 of 13	2		ENSP00000396995.3	Q8NDF8-5
TENT4B	ENST00000562717.1 link	n.-205A>G		upstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151298

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000347

AC:

AN:

1381930

Hom.:

Cov.:

AF XY:

0.0000352

AC XY:

AN XY:

681924

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000436

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151298

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73892

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.290A>G (p.N97S) alteration is located in exon 2 (coding exon 2) of the PAPD5 gene. This alteration results from a A to G substitution at nucleotide position 290, causing the asparagine (N) at amino acid position 97 to be replaced by a serine (S). 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

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.011

.;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.82

T;T

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.069

T;T

MetaSVM

Benign

-0.99

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.40

N;N

REVEL

Benign

0.063

Sift

Uncertain

0.016

D;T

Sift4G

Benign

0.54

T;T

Vest4

0.045

MVP

0.28

MPC

1.3

ClinPred

0.15

GERP RS

1.5

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over