Genetic Variant TENT5C:p.Leu93Val (chr1-117623145-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017709.4(TENT5C):c.277C>G(p.Leu93Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,614,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

TENT5C
NM_017709.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.00

Publications

1 publications found

Variant links:

Genes affected

TENT5C (HGNC:24712): (terminal nucleotidyltransferase 5C) Enables RNA adenylyltransferase activity. Involved in mRNA stabilization. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TENT5C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17416787).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017709.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENT5C	NM_017709.4	MANE Select	c.277C>G	p.Leu93Val	missense	Exon 2 of 2	NP_060179.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TENT5C	ENST00000369448.4	TSL:1 MANE Select	c.277C>G	p.Leu93Val	missense	Exon 2 of 2	ENSP00000358458.3	Q5VWP2
TENT5C	ENST00000880490.1		c.277C>G	p.Leu93Val	missense	Exon 3 of 3	ENSP00000550549.1
TENT5C	ENST00000880491.1		c.277C>G	p.Leu93Val	missense	Exon 2 of 2	ENSP00000550550.1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000517

AC:

AN:

251486

AF XY:

0.0000515

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33480

American (AMR)

AF:

0.000201

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1112012

Other (OTH)

AF:

0.0000662

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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:

0.0000526

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41436

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00316

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68038

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

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:

0.0000282

Hom.:

Bravo

AF:

0.0000604

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

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

Benign

0.099

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.17

Eigen

Benign

-0.11

Eigen_PC

Benign

0.074

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.0051

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

PhyloP100

2.0

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-2.0

REVEL

Benign

0.092

Sift

Benign

0.21

Sift4G

Benign

0.20

Polyphen

0.0040

Vest4

0.30

MVP

0.14

MPC

0.60

ClinPred

0.10

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.54

gMVP

0.41

Mutation Taster

=51/49

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over