Genetic Variant TENT4B:p.Ala135Ser (chr16-50154024-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001365324.3(TENT4B):c.403G>T(p.Ala135Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,381,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A135P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

TENT4B
NM_001365324.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.23

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.118032485).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365324.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TENT4B	NM_001365324.3	MANE Select	c.403G>T	p.Ala135Ser	missense	Exon 1 of 12	NP_001352253.1	A0A7N4YH79
TENT4B	NM_001040284.3		c.358G>T	p.Ala120Ser	missense	Exon 2 of 13	NP_001035374.2	Q8NDF8-5
TENT4B	NM_001365323.2		c.343G>T	p.Ala115Ser	missense	Exon 2 of 13	NP_001352252.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TENT4B	ENST00000561678.7	TSL:5 MANE Select	c.403G>T	p.Ala135Ser	missense	Exon 1 of 12	ENSP00000455837.3	A0A7N4YH79
TENT4B	ENST00000436909.8	TSL:2	c.358G>T	p.Ala120Ser	missense	Exon 2 of 13	ENSP00000396995.3	Q8NDF8-5
TENT4B	ENST00000562717.1	TSL:5	n.-137G>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.24e-7

AC:

AN:

1381380

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

681594

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31420

American (AMR)

AF:

0.00

AC:

AN:

35504

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25086

East Asian (EAS)

AF:

0.00

AC:

AN:

35616

South Asian (SAS)

AF:

0.00

AC:

AN:

78894

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

9.28e-7

AC:

AN:

1077944

Other (OTH)

AF:

0.00

AC:

AN:

57804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.011

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.093

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

PhyloP100

2.2

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.20

REVEL

Benign

0.036

Sift

Benign

0.031

Sift4G

Benign

0.21

Vest4

0.17

MVP

0.52

MPC

1.1

ClinPred

0.085

GERP RS

1.4

gMVP

0.19

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over