dbSNP rs547285140: TENT4B:p.Arg2Trp (chr16-50152956-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001040284.3(TENT4B):c.4C>T(p.Arg2Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000187 in 1,506,378 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

TENT4B
NM_001040284.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.36

Publications

3 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:

ENSG00000260381 (HGNC:):

ENSG00000260381 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005327463).

BS2

High AC in GnomAd4 at 43 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040284.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TENT4B	NM_001040284.3	c.4C>T	p.Arg2Trp	missense	Exon 1 of 13	NP_001035374.2	Q8NDF8-5
TENT4B	NM_001040285.3	c.4C>T	p.Arg2Trp	missense	Exon 1 of 13	NP_001035375.2
TENT4B	NM_001365323.2	c.-110C>T		5_prime_UTR	Exon 1 of 13	NP_001352252.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENT4B	ENST00000436909.8	TSL:2	c.4C>T	p.Arg2Trp	missense	Exon 1 of 13	ENSP00000396995.3	Q8NDF8-5
	ENSG00000260381	ENST00000832509.1		n.104G>A		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.000287

AC:

AN:

149590

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000662

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00828

Gnomad SAS

AF:

0.000212

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000613

AC:

AN:

109314

AF XY:

0.000398

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00878

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000242

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000175

AC:

238

AN:

1356658

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

115

AN XY:

669290

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28912

American (AMR)

AF:

0.00

AC:

AN:

33474

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24270

East Asian (EAS)

AF:

0.00621

AC:

203

AN:

32676

South Asian (SAS)

AF:

0.000209

AC:

AN:

76676

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5020

European-Non Finnish (NFE)

AF:

0.00000281

AC:

AN:

1065792

Other (OTH)

AF:

0.000283

AC:

AN:

56500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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

AF:

0.000287

AC:

AN:

149720

Hom.:

Cov.:

AF XY:

0.000369

AC XY:

AN XY:

73112

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40910

American (AMR)

AF:

0.0000661

AC:

AN:

15118

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00830

AC:

AN:

4942

South Asian (SAS)

AF:

0.000212

AC:

AN:

4708

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10046

Middle Eastern (MID)

AF:

0.00

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67292

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000131

Hom.:

Bravo

AF:

0.000480

ExAC

AF:

0.000238

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

2.8

(source)

DANN

Benign

0.89

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.36

M_CAP

Benign

0.054

MetaRNN

Benign

0.0053

MetaSVM

Benign

-1.0

PhyloP100

-1.4

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.64

REVEL

Benign

0.036

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.013

Vest4

0.17

MutPred

0.33

Loss of methylation at R6 (P = 0.0135)

MVP

0.082

MPC

1.3

ClinPred

0.093

GERP RS

-0.79

PromoterAI

-0.24

Neutral

(source)

gMVP

0.29

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over