Genetic Variant TEP1:p.Glu2498Lys (chr14-20369508-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_007110.5(TEP1):c.7492G>A(p.Glu2498Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

TEP1
NM_007110.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

Publications

1 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.087978214).

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.7492G>A	p.Glu2498Lys	missense	Exon 53 of 55	NP_009041.2
	TEP1	NM_001319035.2		c.7168G>A	p.Glu2390Lys	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.7492G>A	p.Glu2498Lys	missense	Exon 53 of 55	ENSP00000262715.5	Q99973-1
TEP1	ENST00000556935.5	TSL:1	c.7168G>A	p.Glu2390Lys	missense	Exon 51 of 53	ENSP00000452574.1	G3V5X7
TEP1	ENST00000553365.5	TSL:1	n.609G>A		non_coding_transcript_exon	Exon 6 of 9	ENSP00000450475.1	H0YIY9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000596

AC:

AN:

251482

AF XY:

0.0000441

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.000335

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112002

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000576

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.031

Eigen_PC

Benign

0.014

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.74

M_CAP

Benign

0.015

MetaRNN

Benign

0.088

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.9

PhyloP100

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.48

REVEL

Benign

0.026

Sift

Benign

0.12

Sift4G

Uncertain

0.020

Polyphen

0.0050

Vest4

0.27

MutPred

0.37

Gain of MoRF binding (P = 0.0038)

MVP

0.48

MPC

0.12

ClinPred

0.074

GERP RS

2.9

Varity_R

0.049

gMVP

0.33

Mutation Taster

=90/10

polymorphism

(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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over