Genetic Variant TEP1:p.Val2214Ile (chr14-20373548-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007110.5(TEP1):c.6640G>A(p.Val2214Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,613,844 control chromosomes in the GnomAD database, including 44,660 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 7019 hom., cov: 32)

Exomes 𝑓: 0.22 ( 37641 hom. )

Consequence

TEP1
NM_007110.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.45

Publications

38 publications found

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 Gene-Disease associations (from GenCC):

cerebral palsy
Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia

TEP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011783242).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007110.5. 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
	TEP1	NM_007110.5	MANE Select	c.6640G>A	p.Val2214Ile	missense	Exon 46 of 55	NP_009041.2
	TEP1	NM_001319035.2		c.6316G>A	p.Val2106Ile	missense	Exon 44 of 53	NP_001305964.1	G3V5X7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TEP1	ENST00000262715.10	TSL:1 MANE Select	c.6640G>A	p.Val2214Ile	missense	Exon 46 of 55	ENSP00000262715.5	Q99973-1
TEP1	ENST00000556935.5	TSL:1	c.6316G>A	p.Val2106Ile	missense	Exon 44 of 53	ENSP00000452574.1	G3V5X7
TEP1	ENST00000555008.5	TSL:1	n.4669G>A		non_coding_transcript_exon	Exon 34 of 43	ENSP00000450541.1	G3V2A4

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43946

AN:

151940

Hom.:

7015

Cov.:

show subpopulations

Gnomad AFR

AF:

0.415

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.353

Gnomad ASJ

AF:

0.267

Gnomad EAS

AF:

0.295

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.294

GnomAD2 exomes

AF:

0.263

AC:

66067

AN:

251304

AF XY:

0.254

show subpopulations

Gnomad AFR exome

AF:

0.419

Gnomad AMR exome

AF:

0.376

Gnomad ASJ exome

AF:

0.266

Gnomad EAS exome

AF:

0.295

Gnomad FIN exome

AF:

0.251

Gnomad NFE exome

AF:

0.211

Gnomad OTH exome

AF:

0.260

GnomAD4 exome

AF:

0.221

AC:

323285

AN:

1461786

Hom.:

37641

Cov.:

AF XY:

0.220

AC XY:

160238

AN XY:

727192

show subpopulations

African (AFR)

AF:

0.422

AC:

14140

AN:

33480

American (AMR)

AF:

0.375

AC:

16782

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

7101

AN:

26134

East Asian (EAS)

AF:

0.247

AC:

9803

AN:

39698

South Asian (SAS)

AF:

0.233

AC:

20115

AN:

86256

European-Finnish (FIN)

AF:

0.251

AC:

13395

AN:

53416

Middle Eastern (MID)

AF:

0.309

AC:

1782

AN:

5768

European-Non Finnish (NFE)

AF:

0.203

AC:

225694

AN:

1111940

Other (OTH)

AF:

0.240

AC:

14473

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

15362

30725

46087

61450

76812

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8088

16176

24264

32352

40440

<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:

0.289

AC:

43989

AN:

152058

Hom.:

7019

Cov.:

AF XY:

0.292

AC XY:

21728

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.415

AC:

17207

AN:

41452

American (AMR)

AF:

0.353

AC:

5399

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.267

AC:

927

AN:

3470

East Asian (EAS)

AF:

0.294

AC:

1520

AN:

5178

South Asian (SAS)

AF:

0.237

AC:

1140

AN:

4814

European-Finnish (FIN)

AF:

0.253

AC:

2672

AN:

10576

Middle Eastern (MID)

AF:

0.333

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14229

AN:

67962

Other (OTH)

AF:

0.297

AC:

626

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1569

3138

4707

6276

7845

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.244

Hom.:

14776

Bravo

AF:

0.302

TwinsUK

AF:

0.204

AC:

756

ALSPAC

AF:

0.204

AC:

788

ESP6500AA

AF:

0.410

AC:

1806

ESP6500EA

AF:

0.205

AC:

1767

ExAC

AF:

0.258

AC:

31337

Asia WGS

AF:

0.314

AC:

1089

AN:

3478

EpiCase

AF:

0.224

EpiControl

AF:

0.226

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.073

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.31

MetaRNN

Benign

0.0012

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.81

PhyloP100

1.5

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.40

REVEL

Benign

0.052

Sift

Benign

0.20

Sift4G

Benign

0.19

Polyphen

0.0010

Vest4

0.10

MPC

0.088

ClinPred

0.0025

GERP RS

4.3

PromoterAI

-0.029

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.022

gMVP

0.19

Mutation Taster

=98/2

polymorphism (auto)

(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