Genetic Variant TEP1:p.Thr2043Thr (chr14-20376224-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_007110.5(TEP1):c.6129G>A(p.Thr2043Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0611 in 1,614,100 control chromosomes in the GnomAD database, including 3,336 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.046 ( 227 hom., cov: 32)

Exomes 𝑓: 0.063 ( 3109 hom. )

Consequence

TEP1
NM_007110.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.39

Publications

10 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

new If you want to explore the variant's impact on the transcript NM_007110.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP7

Synonymous conserved (PhyloP=-4.39 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0878 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.6129G>A	p.Thr2043Thr	synonymous	Exon 42 of 55	NP_009041.2
	TEP1	NM_001319035.2		c.5805G>A	p.Thr1935Thr	synonymous	Exon 40 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.6129G>A	p.Thr2043Thr	synonymous	Exon 42 of 55	ENSP00000262715.5	Q99973-1
TEP1	ENST00000556935.5	TSL:1	c.5805G>A	p.Thr1935Thr	synonymous	Exon 40 of 53	ENSP00000452574.1	G3V5X7
TEP1	ENST00000555008.5	TSL:1	n.4158G>A		non_coding_transcript_exon	Exon 30 of 43	ENSP00000450541.1	G3V2A4

Frequencies

GnomAD3 genomes

AF:

0.0462

AC:

7034

AN:

152148

Hom.:

227

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0180

Gnomad AMI

AF:

0.0264

Gnomad AMR

AF:

0.0359

Gnomad ASJ

AF:

0.0723

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0951

Gnomad FIN

AF:

0.0686

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0610

Gnomad OTH

AF:

0.0494

GnomAD2 exomes

AF:

0.0547

AC:

13742

AN:

251154

AF XY:

0.0591

show subpopulations

Gnomad AFR exome

AF:

0.0182

Gnomad AMR exome

AF:

0.0278

Gnomad ASJ exome

AF:

0.0764

Gnomad EAS exome

AF:

0.000598

Gnomad FIN exome

AF:

0.0687

Gnomad NFE exome

AF:

0.0614

Gnomad OTH exome

AF:

0.0552

GnomAD4 exome

AF:

0.0626

AC:

91537

AN:

1461834

Hom.:

3109

Cov.:

AF XY:

0.0640

AC XY:

46530

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.0169

AC:

567

AN:

33480

American (AMR)

AF:

0.0291

AC:

1301

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0761

AC:

1989

AN:

26130

East Asian (EAS)

AF:

0.000327

AC:

AN:

39700

South Asian (SAS)

AF:

0.0930

AC:

8023

AN:

86254

European-Finnish (FIN)

AF:

0.0663

AC:

3539

AN:

53412

Middle Eastern (MID)

AF:

0.0733

AC:

423

AN:

5768

European-Non Finnish (NFE)

AF:

0.0649

AC:

72219

AN:

1111976

Other (OTH)

AF:

0.0573

AC:

3463

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

4715

9430

14146

18861

23576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2730

5460

8190

10920

13650

<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:

0.0462

AC:

7035

AN:

152266

Hom.:

227

Cov.:

AF XY:

0.0471

AC XY:

3509

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0180

AC:

750

AN:

41562

American (AMR)

AF:

0.0358

AC:

548

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0723

AC:

251

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5184

South Asian (SAS)

AF:

0.0950

AC:

458

AN:

4822

European-Finnish (FIN)

AF:

0.0686

AC:

727

AN:

10590

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0610

AC:

4146

AN:

68020

Other (OTH)

AF:

0.0489

AC:

103

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

346

691

1037

1382

1728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<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:

0.0548

Hom.:

280

Bravo

AF:

0.0416

Asia WGS

AF:

0.0350

AC:

122

AN:

3478

EpiCase

AF:

0.0632

EpiControl

AF:

0.0626

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.44

(source)

DANN

Benign

0.58

PhyloP100

-4.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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