Variant chr14-20381934-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007110.5(TEP1):c.4403G>A(p.Cys1468Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,613,728 control chromosomes in the GnomAD database, including 32,302 homozygotes. 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.25 ( 5407 hom., cov: 32)

Exomes 𝑓: 0.19 ( 26895 hom. )

Consequence

TEP1
NM_007110.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.373

Variant links:

Genes affected

TEP1 (HGNC:11726): (telomerase associated protein 1) This gene product is a component of the ribonucleoprotein complex responsible for telomerase activity which catalyzes the addition of new telomeres on the chromosome ends. The telomerase-associated proteins are conserved from ciliates to humans. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

TEP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032809973).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEP1	NM_007110.5 linkuse as main transcript	c.4403G>A	p.Cys1468Tyr	missense_variant	30/55	ENST00000262715.10	NP_009041.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEP1	ENST00000262715.10 linkuse as main transcript	c.4403G>A	p.Cys1468Tyr	missense_variant	30/55	1	NM_007110.5	ENSP00000262715	P1	Q99973-1

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37290

AN:

151912

Hom.:

5396

Cov.:

show subpopulations

Gnomad AFR

AF:

0.407

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.194

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.184

Gnomad OTH

AF:

0.229

GnomAD3 exomes

AF:

0.197

AC:

49396

AN:

250592

Hom.:

5500

AF XY:

0.194

AC XY:

26277

AN XY:

135432

show subpopulations

Gnomad AFR exome

AF:

0.412

Gnomad AMR exome

AF:

0.175

Gnomad ASJ exome

AF:

0.239

Gnomad EAS exome

AF:

0.0991

Gnomad SAS exome

AF:

0.195

Gnomad FIN exome

AF:

0.193

Gnomad NFE exome

AF:

0.187

Gnomad OTH exome

AF:

0.198

GnomAD4 exome

AF:

0.186

AC:

272410

AN:

1461698

Hom.:

26895

Cov.:

AF XY:

0.186

AC XY:

135353

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.420

Gnomad4 AMR exome

AF:

0.177

Gnomad4 ASJ exome

AF:

0.241

Gnomad4 EAS exome

AF:

0.100

Gnomad4 SAS exome

AF:

0.191

Gnomad4 FIN exome

AF:

0.189

Gnomad4 NFE exome

AF:

0.180

Gnomad4 OTH exome

AF:

0.194

GnomAD4 genome

AF:

0.246

AC:

37331

AN:

152030

Hom.:

5407

Cov.:

AF XY:

0.243

AC XY:

18051

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.407

Gnomad4 AMR

AF:

0.192

Gnomad4 ASJ

AF:

0.240

Gnomad4 EAS

AF:

0.101

Gnomad4 SAS

AF:

0.201

Gnomad4 FIN

AF:

0.194

Gnomad4 NFE

AF:

0.184

Gnomad4 OTH

AF:

0.235

Alfa

AF:

0.193

Hom.:

7591

Bravo

AF:

0.252

TwinsUK

AF:

0.170

AC:

631

ALSPAC

AF:

0.182

AC:

703

ESP6500AA

AF:

0.379

AC:

1672

ESP6500EA

AF:

0.184

AC:

1579

ExAC

AF:

0.203

AC:

24696

Asia WGS

AF:

0.215

AC:

752

AN:

3478

EpiCase

AF:

0.183

EpiControl

AF:

0.191

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.50

DEOGEN2

Benign

0.062

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.13

T;T

MetaRNN

Benign

0.0033

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-2.8

N;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Uncertain

0.58

PROVEAN

Benign

3.6

N;N

REVEL

Benign

0.096

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.11

MPC

0.19

ClinPred

0.0087

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.053

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over