Genetic Variant TENT4B:p.Ser62Arg (chr16-50153807-C-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.186C>G(p.Ser62Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000824 in 1,213,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000047 ( 0 hom. )

Consequence

TENT4B
NM_001365324.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20437816).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENT4B	NM_001365324.3 link	c.186C>G	p.Ser62Arg	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 link	c.186C>G	p.Ser62Arg	missense_variant	Exon 1 of 12	5	NM_001365324.3	ENSP00000455837.3		A0A7N4YH79
TENT4B	ENST00000436909.8 link	c.141C>G	p.Ser47Arg	missense_variant	Exon 2 of 13	2		ENSP00000396995.3		Q8NDF8-5

Frequencies

GnomAD3 genomes

AF:

0.0000335

AC:

AN:

149044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000200

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:

0.00

Gnomad OTH

AF:

0.000487

GnomAD4 exome

AF:

0.00000470

AC:

AN:

1064656

Hom.:

Cov.:

AF XY:

0.00000394

AC XY:

AN XY:

507976

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000131

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:

0.00000110

Gnomad4 OTH exome

AF:

0.0000719

GnomAD4 genome

AF:

0.0000335

AC:

AN:

149044

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

72608

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.000200

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000487

Bravo

AF:

0.0000907

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.141C>G (p.S47R) 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 141, causing the serine (S) at amino acid position 47 to be replaced by an arginine (R). 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

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.41

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.2

REVEL

Benign

0.072

Sift

Pathogenic

0.0

Sift4G

Benign

0.13

Vest4

0.15

MutPred

0.28

Loss of phosphorylation at S47 (P = 0.0013);

MVP

0.12

MPC

1.4

ClinPred

0.93

GERP RS

2.1

gMVP

0.12

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