Genetic Variant NM_007110.5:c.7458C>G (chr14-20369542-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.591

Publications

42 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 -20 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 VariationId is 1232563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 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.7458C>G	p.Ile2486Met	missense	Exon 53 of 55	NP_009041.2
	TEP1	NM_001319035.2		c.7134C>G	p.Ile2378Met	missense	Exon 51 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.7458C>G	p.Ile2486Met	missense	Exon 53 of 55	ENSP00000262715.5	Q99973-1
TEP1	ENST00000556935.5	TSL:1	c.7134C>G	p.Ile2378Met	missense	Exon 51 of 53	ENSP00000452574.1	G3V5X7
TEP1	ENST00000553365.5	TSL:1	n.575C>G		non_coding_transcript_exon	Exon 6 of 9	ENSP00000450475.1	H0YIY9

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

GnomAD2 exomes

AF:

0.267

AC:

67149

AN:

251386

AF XY:

0.258

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 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

African (AFR)

AF:

0.461

AC:

15436

AN:

33480

American (AMR)

AF:

0.379

AC:

16967

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.266

AC:

6959

AN:

26134

East Asian (EAS)

AF:

0.247

AC:

9802

AN:

39700

South Asian (SAS)

AF:

0.235

AC:

20235

AN:

86252

European-Finnish (FIN)

AF:

0.251

AC:

13399

AN:

53420

Middle Eastern (MID)

AF:

0.311

AC:

1792

AN:

5768

European-Non Finnish (NFE)

AF:

0.206

AC:

229410

AN:

1111908

Other (OTH)

AF:

0.243

AC:

14653

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

14880

29760

44640

59520

74400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8206

16412

24618

32824

41030

<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:

0.303

AC:

45980

AN:

151840

Hom.:

7855

Cov.:

AF XY:

0.306

AC XY:

22700

AN XY:

74178

show subpopulations

African (AFR)

AF:

0.458

AC:

18938

AN:

41372

American (AMR)

AF:

0.360

AC:

5478

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

912

AN:

3470

East Asian (EAS)

AF:

0.295

AC:

1520

AN:

5160

South Asian (SAS)

AF:

0.240

AC:

1154

AN:

4804

European-Finnish (FIN)

AF:

0.255

AC:

2691

AN:

10552

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.212

AC:

14379

AN:

67948

Other (OTH)

AF:

0.304

AC:

637

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1563

3126

4689

6252

7815

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

438

876

1314

1752

2190

<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:

0.214

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.14

DEOGEN2

Benign

0.047

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.10

MetaRNN

Benign

0.00047

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.8

PhyloP100

0.59

PrimateAI

Benign

0.32

PROVEAN

Benign

0.47

REVEL

Benign

0.012

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.10

MPC

0.11

ClinPred

0.00059

GERP RS

2.8

Varity_R

0.025

gMVP

0.11

Mutation Taster

=100/0

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