Variant 14-20369542-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_007110.5(TEP1):c.7458C>G(p.Ile2486Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,613,600 control chromosomes in the GnomAD database, including 46,967 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.30 ( 7855 hom., cov: 31)

Exomes 𝑓: 0.22 ( 39112 hom. )

Consequence

TEP1
NM_007110.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.591

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.7031045E-4).

BP6

Variant 14-20369542-G-C is Benign according to our data. Variant chr14-20369542-G-C is described in ClinVar as [Benign]. Clinvar id is 1232563.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEP1	NM_007110.5 linkuse as main transcript	c.7458C>G	p.Ile2486Met	missense_variant	53/55	ENST00000262715.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEP1	ENST00000262715.10 linkuse as main transcript	c.7458C>G	p.Ile2486Met	missense_variant	53/55	1	NM_007110.5	P1	Q99973-1

Frequencies

GnomAD3 genomes

AF:

0.303

AC:

45945

AN:

151722

Hom.:

7849

Cov.:

show subpopulations

Gnomad AFR

AF:

0.458

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.359

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.296

Gnomad SAS

AF:

0.241

Gnomad FIN

AF:

0.255

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.301

GnomAD3 exomes

AF:

0.267

AC:

67149

AN:

251386

Hom.:

9897

AF XY:

0.258

AC XY:

35058

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.458

Gnomad AMR exome

AF:

0.379

Gnomad ASJ exome

AF:

0.260

Gnomad EAS exome

AF:

0.295

Gnomad SAS exome

AF:

0.235

Gnomad FIN exome

AF:

0.251

Gnomad NFE exome

AF:

0.214

Gnomad OTH exome

AF:

0.261

GnomAD4 exome

AF:

0.225

AC:

328653

AN:

1461760

Hom.:

39112

Cov.:

AF XY:

0.224

AC XY:

162727

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.461

Gnomad4 AMR exome

AF:

0.379

Gnomad4 ASJ exome

AF:

0.266

Gnomad4 EAS exome

AF:

0.247

Gnomad4 SAS exome

AF:

0.235

Gnomad4 FIN exome

AF:

0.251

Gnomad4 NFE exome

AF:

0.206

Gnomad4 OTH exome

AF:

0.243

GnomAD4 genome

AF:

0.303

AC:

45980

AN:

151840

Hom.:

7855

Cov.:

AF XY:

0.306

AC XY:

22700

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.458

Gnomad4 AMR

AF:

0.360

Gnomad4 ASJ

AF:

0.263

Gnomad4 EAS

AF:

0.295

Gnomad4 SAS

AF:

0.240

Gnomad4 FIN

AF:

0.255

Gnomad4 NFE

AF:

0.212

Gnomad4 OTH

AF:

0.304

Alfa

AF:

0.214

Hom.:

2836

Bravo

AF:

0.316

TwinsUK

AF:

0.207

AC:

766

ALSPAC

AF:

0.209

AC:

806

ESP6500AA

AF:

0.437

AC:

1925

ESP6500EA

AF:

0.207

AC:

1780

ExAC

AF:

0.263

AC:

31913

Asia WGS

AF:

0.314

AC:

1091

AN:

3478

EpiCase

AF:

0.226

EpiControl

AF:

0.230

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2020

This variant is associated with the following publications: (PMID: 19766477) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

Cadd

Benign

Dann

Benign

0.14

DEOGEN2

Benign

0.047

T;T

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.10

T;T

MetaRNN

Benign

0.00047

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.8

N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.32

PROVEAN

Benign

0.47

N;N

REVEL

Benign

0.012

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.10

MPC

0.11

ClinPred

0.00059

GERP RS

2.8

Varity_R

0.025

gMVP

0.11

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