dbSNP rs2104978: TEP1:p.His2562Arg (chr14-20368874-T-C) – 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.7685A>G(p.His2562Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0622 in 1,613,536 control chromosomes in the GnomAD database, including 3,450 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 0.045 ( 219 hom., cov: 32)

Exomes 𝑓: 0.064 ( 3231 hom. )

Consequence

TEP1
NM_007110.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.04

Publications

18 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004953891).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.083 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.7685A>G	p.His2562Arg	missense	Exon 54 of 55	NP_009041.2
	TEP1	NM_001319035.2		c.7361A>G	p.His2454Arg	missense	Exon 52 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.7685A>G	p.His2562Arg	missense	Exon 54 of 55	ENSP00000262715.5	Q99973-1
TEP1	ENST00000556935.5	TSL:1	c.7361A>G	p.His2454Arg	missense	Exon 52 of 53	ENSP00000452574.1	G3V5X7
TEP1	ENST00000553365.5	TSL:1	n.*49A>G		non_coding_transcript_exon	Exon 7 of 9	ENSP00000450475.1	H0YIY9

Frequencies

GnomAD3 genomes

AF:

0.0449

AC:

6823

AN:

151976

Hom.:

219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.0242

Gnomad AMR

AF:

0.0334

Gnomad ASJ

AF:

0.0490

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0899

Gnomad FIN

AF:

0.0695

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0639

Gnomad OTH

AF:

0.0420

GnomAD2 exomes

AF:

0.0530

AC:

13305

AN:

250980

AF XY:

0.0572

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.0258

Gnomad ASJ exome

AF:

0.0522

Gnomad EAS exome

AF:

0.000598

Gnomad FIN exome

AF:

0.0701

Gnomad NFE exome

AF:

0.0628

Gnomad OTH exome

AF:

0.0516

GnomAD4 exome

AF:

0.0640

AC:

93499

AN:

1461442

Hom.:

3231

Cov.:

AF XY:

0.0650

AC XY:

47264

AN XY:

727010

show subpopulations

African (AFR)

AF:

0.00974

AC:

326

AN:

33476

American (AMR)

AF:

0.0272

AC:

1215

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.0532

AC:

1391

AN:

26130

East Asian (EAS)

AF:

0.000327

AC:

AN:

39696

South Asian (SAS)

AF:

0.0886

AC:

7637

AN:

86196

European-Finnish (FIN)

AF:

0.0677

AC:

3617

AN:

53392

Middle Eastern (MID)

AF:

0.0675

AC:

389

AN:

5762

European-Non Finnish (NFE)

AF:

0.0678

AC:

75420

AN:

1111720

Other (OTH)

AF:

0.0578

AC:

3491

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

4232

8464

12696

16928

21160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2826

5652

8478

11304

14130

<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:

0.0449

AC:

6823

AN:

152094

Hom.:

219

Cov.:

AF XY:

0.0460

AC XY:

3424

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0119

AC:

494

AN:

41464

American (AMR)

AF:

0.0334

AC:

511

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0490

AC:

170

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5170

South Asian (SAS)

AF:

0.0900

AC:

434

AN:

4822

European-Finnish (FIN)

AF:

0.0695

AC:

735

AN:

10576

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0639

AC:

4341

AN:

67986

Other (OTH)

AF:

0.0416

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

335

670

1006

1341

1676

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:

0.0561

Hom.:

1153

Bravo

AF:

0.0397

Asia WGS

AF:

0.0350

AC:

121

AN:

3476

EpiCase

AF:

0.0636

EpiControl

AF:

0.0613

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0050

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

4.0

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.0

REVEL

Benign

0.21

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Varity_R

0.31

gMVP

0.24

Mutation Taster

=95/5

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

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

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